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XMRV ¿LA PANDEMIA QUE VIENE? Por Jose Luis Licenciado en Farmacia Noviembre 2009 La NOTICIA Los científicos del Whittemore Peterson Institute (WPI), institución que se dedica a la investigación de enfermedades neuroinmunológicas en Reno (Nevada, Usa), conjuntamente con el Instituto Nacional del Cancer y la Clínica de Cleveland anunciaban un hito: Habían descubierto un retrovirus en las muestras de sangre de la mayoría de los afectados por el SFC. El estudio que publicó la revista Science el 9 de octubre del 2009, demostraba que un retrovirus llamado XMRV (Xenotrophic Murine Related Virus), estaba en la sangre de 68 de 101 afectados (67%) de SFC estudiados,comparado con 8 de 218 personas sanas. (3.7 %) Estos primeros datos hacian mención al ADN, que fue lo que se publico en Science. Estudios posteriores prueban una prevalencia casi total (98%) de la siguiente manera: 19 de 33 pacientes tenían anticuerpos del XMRV 30 de 33 pacientes tenían virus con capacidad de contagio en el plasma 10 de 33 pacientes tenían proteinas del XMRV "They don't have active virus," Mikovits explained, "but they have antibodies," suggesting that there are patients who are infected with XMRV but whose infections cannot be detected by standard methods because they are latent. Latent virus might also explain why CFS is a relapsing-remitting disease and why some individuals are much more strongly affected than others. Los Precedentes Robert H. Silverman, Ph.D., profesor del Departamento de Cancer Biology en la Cleveland Clinic Lerner Research Institute, fue el que descubrió, hace tres años, el XMRV en el tejido de cáncer de próstata de hombres que tenían un desarreglo genético e inmunológico muy específico, la vía de la RNasa. Este mismo desarreglo inmunológico lo tienen algunos enfermos del SFC, y por eso la Dra. Judy Mikovits del WPI decidió enviar muestras de sangre de personas enfermas con el SFC buscando resultados. XMRV en cancer de próstata. Laboratorio Ila Singh. Universidad de Utah El RETROVIRUS El XMRV es un gamma retrovirus, sobre todo estudiado en ratones pero no se sabía que podía infectar a los seres humanos. En los animales, este virus provoca desarreglos neurológicos, insuficiencia inmunológica, linfomas y leucemia. Se trata por tanto del cuarto retrovirus que exógeno que puede infectar a la especie humana, después del VIH, el HTLV-1 y el HTLV-2 (que causan linfomas y enfermedades neurodegenerativas) A diferencia del VIH retrovirus complejo de la familia de los lentisvirus, el XMRV pertenece a los retrovirus simples familia gammaretrovirus, y por tanto con una capacidad de mutación menor que el VIH, lo que sobre el papel lo convierte en mejor candidato para una posible vacuna. El virus ha sido encontrado en el interior de los linfocitos B y T, aunque se postula que podría hallarse tambien dentro de las NK. La CONTAGIOSIDAD Las vias de contagio parecen ser las mismas que las del VIH, es decir por sangre o plasma, fluidos corporales (semen, flujo) y se ha postulado que la carga viral en saliva podría ser suficientemente elevada para provocar contagios (a diferencia del VIH) Se ha comprobado que linfocitos infectados son capaces de infectar a linfocitos sanos y que los contagios se puden dar tambien a través del plasma sanguíneo. Esto es lo que dicen los del WPI: “XMRV is thought to be transmitted through body fluids such as blood, semen, and mother’s breast milk but is not transmitted through the air. It is not known whether XMRV is more easily transmitted than other human retroviruses.” (Ver recomendaciones sobre transfusiones y bancos de sangre más adelante) El Sistema Inmunitario y los oportunistas Innumerables son los estudios que han encontrado anomalias en el sistema inmunitario. Principalmente se han encontrado una baja actividad de las NK, así como un aumento de las citoquinas proinflamatorias y una desregulación hacia un tipo de inmunidad humoral (Th2) vs la celular (Th1). Dicha desregulación provocaría que ciertos virus sobretodo del tipo Herpesvirus, pasasen a un estadio de reactivación. Entre ellos nos encontramos elvados títulos de IgG’s para EBV, CMV, HHV-6, HHV-7, así como de enterovirus (Coxaquie) y parvovirus B19. (Ver más información sobre el sistema inmunitario más adelante) El Cáncer La Incidencia del Cancer en enfermos de SFC es anormalmente elevada y a edades tempranas (sobre los 45 años). Sobretodo son muy comunes los limfonas no Hodgkin de cel de manto (en un 20%) y ciertos tumores relacionados con el tiroides (el 7% de enfermos de SFC) , testículos y ovarios. De hecho, el XMRV se ha encontrado en el interior de los linfocitos y en un reciente estudio del Dr Silverman ha encontrado que se activa en presencia de DHT (Dihidrotestosterona). Se ha publicado esto recientemente: J Virol. 2009 Nov 11. [Epub ahead of print] Androgen Stimulates Transcription and Replication of XMRV (Xenotropic Murine Leukemia Virus-Related Virus). Dong B, Silverman RH. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. XMRV is a gammaretrovirus originally identified in a subset of prostate cancer patients. Because androgens stimulate prostate tumors and some retroviruses, we investigated effects of dihydrotestosterone (DHT) on XMRV transcription and replication. Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but only in cells containing a functional androgen receptor. Mutations in the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiveness. Furthermore, DHT stimulated XMRV replication by 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV LTR into host DNA could impart androgen stimulation on cellular genes. Parece ser que el Cortisol elevado provocaría una reactiviación del virus que pasaría del estado de latencia al funcional. Asimismo parece ser que también la progesterona sería un activador del mismo, según dijo la Dra Mikovitz: “Well, cortisol, progesterone and viruses turn on the virus, according to Mikovitz. She also theorized that a vaccine might turn it on too.” La activación del virus por el cortisol podría perfectamente explicar que el inicio de la enfermedad viniera siempre precedido por un periodo de estrés constante y elevado. EL XMRV en OTRAS PATOLOGIAS El virus también se encuentra en una pequeña muestra de niños con AUTISMO en un 40%, en Fibromialgia en un 60%, y en Esclerosis Multiple. Dra Mikovitz ha teorizado en cuanto al autismo en niños, diciendo que la bateria de vacunas obligatorias que le son administradas a los bebes en los primeros meses de vida, podrían actuar como detonante en la replicación del virus XMRV que se encontraría dentro de los linfocitos. (ver más información sobre autismo y SFC en niños más adelante) La más que probable causalidad entre XMRV y SFC El 98% de los enfermos con SFC tenían el ADN, proteinas, virus, o anticuerpos, lo cual son datos impresionantes. Por otro lado alrededor de un 4% de controles sanos también dieron positivos lo que les convierte en potenciales diseminadores de la enfermedad ya que no manifiestan clínica, todo y que la incidencia en dichos portadores de determinados canceres y cardiopatias isquémicas podría ser superior al de la población general. Pero, ¿por qué hay personas que desarrollan el SFC y otros no? La mayoria de enfermos inician su patologia como consecuencia de un factor estresante, que sería el desencadenante de una cascada de sintomas que afectan a diferentes organos y sistemas. Se ha reportado que el estrés laboral continuado, una operación, una intoxicación por metales pesados (Hg) pudieron ser los desencadenates de la patología. Multiples de los relatos la asocian con una mononucleosis que ya nunca remitió. Según el Dr Peterson, un mecanismo posible sería: “Teoría del factor X”. Primer paso: Infección con XMRV. Ni idea de cómo ocurre. Podría ser que el pequeño XMRV viaja a caballo de algún enorme y pesado herpesvirus, como el Epstein-Barr, o el HHV6. Se sabe que esto ocurre, pero hay muchas más posibilidades. Segundo paso: Infección de los linfocitos B y T y las células NK. La dra. Klimas dijo que más del 70% de los linfocitos están “activados”, algo está pasando. Paso tercero: Desequilibrio entre el número de células NK y su actividad. A causa de la infección retroviral, las células NK se desequilibran. Esto es similar a lo que ocurre en la enfermedad del VIH con los linfocitos CD4. Da como resultado unas células NK pobres y poco funcionales (y otros problemas con las células T y B) la persona ahora tiene una inmunodeficiencia. Las células NK son importantes en el control de los virus, herpes y otros agentes. Paso cuarto: Reactivación de otros agentes. Carga viral incrementada de Epsteinbar y otros agentes, provocan una producción de citokinas, activación de la Sintetasa 2 – 5 A, RNAsa L la cual aumenta los síntomas. Es interesante darse cuenta que los pacientes de SIDA se sienten mejor con la supresión de las infecciones secundarias. Esto explicaría porqué los tratamientos con antibióticos, antivirales y gammaglobulina y otros agentes hacen que algunos pacientes con SFC se sientan mejor durante un tiempo (ej tratamientos con Valtrex, Valcyte o Vistide consiguen mejoras relativas según estudios de los Drs Lerner y Montoya) EL Estudio Noruego: RITUXIMAB El pasado verano en un pequeño hospital Noruego de la Universidad de Haukeland el Dr Olaf Mella y col y de manera fortuita detectan que en un paciente con SFC tratado con Metotrexato como parte del tratamiento contra un linfoma, mejora de forma radical a las pocas semanas de haberselo administrado. Dicha mejora es temporal, y remite al cabo de unos 4 meses. Posteriormente es tratado con Rituximab (Mabthera, Roche) que es un anticuerpo quimérico utlizado para el tratamiento de linfoma de Hodgkin’s que provoca una depleción selectiva de los linfocitos C19 y se reproduce la misma recuperación al tiempo que desparece en sangre la concentración de dichos linfocitos. La prueba es repetida con 3 enfermos con SFC, y en los 3 se produce una espectacular mejoría al provocar la desaparición en sangre de dichos linfocitos. Actualmente están llevando a cabo un estudio con un mayor número de pacientes, sobre los que tambien se les determinará la presencia del XMRV. Aunque no sería la forma de tratar el SFC debido a los posibles efectos adversos (reactivación de determinados patógenos, como un virus endogeno cerebral mortal) –todo y que se ha utilizado en artritis reumatoidea con ciertos beneficios- si que nos da “las pistas” de que un posible patógeno que “vive” dentro de los linfocitos sea el causante directo o indirecto (ej autoanticuerpos) de la sintomatologia del SFC. Por tanto no sería descabellado postular que al eliminar los linfocitos tambien eliminásemos de forma temporal parte de los virus que los “habitan” (el XMRV, EBV etc) bajando la carga viral y normalizase la hiperrespuesta inmune que conducirían a una desapareción temporal de la sintomatologia característica del SFC. Esto es lo que se muestra en la gráfica. Los pacientes 1 y 2 presentan sendas patologias autoinmunes (autotiroidismo y diabetes) y una clínica máyor, mientras que el paciente 3 no presenta ninguna patologia de base y una SFC moderado. Los Bancos de Sangre El 30 de Octubre la Oficina de Salud Pública y Ciencia de los Estados Unidos emite un comunicado (se muestra íntegro en los anexos) en el que hace mención al nuevo retrovirus y dice textualmente: “(…) the finding that the virus is associated with white blood cells has led some to question whether XMRV could be transmitted by transfusion and might therefore pose a threat to the health of blood recipients and potentially also transplant recipients.” “The HHS Blood Safety Committee works with all the PHS agencies (i.e., CDC, FDA, HRSA, and NIH) to ensure the safety and availability of blood products as well as transplantation safety. Under the leadership of that committee, steps are being taken to investigate the blood safety threat from XMRV and the potentially protective role of white cell removal, which is performed on approximately 70% of blood. An interagency Emerging Infectious Diseases working group that reports to the Blood Safety Committee is currently assessing the literature on XMRV, conducting meetings with experts on this retrovirus, and interacting with groups that could study the question of blood safety. A report is expected within several weeks. In particular, the National Heart Lung and Blood Institute Retrovirus Epidemiology Donor Study-II (REDS-II) investigators are aware of the report in Science and are assessing the prevalence of XMRV in blood donors to determine whether studies aimed at evaluating transfusiontransmission rate are warranted using NHLBI's repositories of donor and recipient blood samples“ Por otro lado La Asociación ME escribió a Sir Liam Donaldson, Director Médico delDepartamento de Salud de UK, en octubre, en relación con la investigación XMRV - en particular, de la situación respecto a la donación de sangre y servicios de transfusión de sangre aquí en el Reino Unido (se puede ver la totalidad de la carta más adelante) “The Standing Advisory Committee on Transfusion Transmitted Infections (SACTTI), part of UK Blood Services, will be producing a risk assessment for this virus. The current advice from UK Blood Services in relation to ME/CFS has been further clarified: Individuals suffering from ME/CFS are deferred from blood donation until their condition has resolved and they are feeling completely well. The research has also been drawn to the attention of the secretariats for the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) and the National Expert Panel on New and Emerging Infections (NEPNEI), who will continue to monitor developments in conjunction with UK Blood Services and the Health Protection Agency. A copy of the MEA letter and information on XMRV has also been passed to the Professional Director of the UK Blood Services Joint Professional Advisory Committee, along with all the UK virology and retrovirology experts who were copied into our original correspondence.” La cruz roja japonosa emitió un comunicado en el que reconoce que en un muestreo efectuado en los bancos de sangre se ha encotrado una baja incidencia del XMRV, aunque no han comentado en qué porcentaje. Los TEST La detección del nuevo retrovirus fue gracias al Virochip que contiene más de 22000 secuencias de ADN de todos los virus conocidos. Se utiliza para identificar virus raros y poco comunes. Actualmente los laboratorios VIP Dx en Reno Nevada ofertan una prueba por PCR para la detección del AND del virus, lo que representaria una infección activa o una determinación de Anticuerpos que expresaria el “contacto” previo con el virus. Aparte del económico, el único problema es el logístico ya que las muestras de sangre deberían de llegar a Reno en max 24 horas, y eso desde Europa es más que poco probable. Hay un par de laboratorios en Europa que probablemente ofertaran la prueba en unos meses, uno en Belgica y otro en UK. Asimismo el Instituto Whittemore Peterson esta semana ha “abierto sus puertas” en el sentido que ha ofrecido a través de su pagina Web la oportunidad de poder inscribirse a través de un formulario como voluntario para realizar donaciones de sangre y poder participar en un futuro en investigaciones con medicamentos contra el XMRV y para poder restaurar la salud de los enfermos de SFC. Los POSIBLES TRATAMIENTOS Al tratarse de un retrovirus se podria utilizar la experiencia en el desarrollo de antiretrovirales desarrollada durante años para el tratamiento del VIH. Según Mikovitz: "can imagine a number of combination therapies that could be quite effective and could at least be used in clinical trials right away". Los antiretrovirales que se manejan son Inhibidores de la transcriptasa inversa (Interlence, rescriptor, sustiva, viramisine) inhibidores de la integrasa (Isentris) o inhibidores de la proteosoma (bortezomib). Tambien se ha hablado, incluso parece ser que algunos medicos ya han iniciado tratamientos con AZT. “She included AIDS drugs such as reverse transcriptase inhibitors and integrase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) and cancer fighting proteasome inhibitors. Dr. Klimas, an AID's and ME/CFS researcher and physician stated that "The good news is that if XMRV is linked to C.F.S., there are many antiviral drugs that have already been safety tested in H.I.V. that may inhibit viral replication." The WPI will be assessing the effectiveness of different drug therapies in some ME/CFS patients.” “Two anti-HIV strategies that do have promise for XMRV are integrase inhibitors and nonnucleoside reverse transcriptase inhibitors. Due to the details of how XMRV is activated, nonsteroidal anti-inflammatory drugs and Velcade (bortezomib, Millennium) also may be candidates for treatment.” Obviamente la especificidad de estos medicamentos los podria hacer del todo inútiles, pero existe gran cantidad de “prototipos” desechados que se podrían reconsiderar y que ahorrarian mucho tiempo de desarrollo. “Because we have so many FDA approved antiretrovirals particularly non nucleoside RT inhibitors and integrase inhibitors as well as non steroidal antinflammatories. We see great promise of combination therapeutic strategies very quickly. If an individual gets the immune system modulated to control and silence the virus the one can be well .The goal is to keep the virus quiet and the homeostasis as with the elite controllers of HIV. There are two GRE sites in the CIA acting elements of the virus. These respond to hormones and cortisol. By definition every positive patient is an AIDS patient” Según Mikovitz como no puede exisitir SIDA sin VIH, tampoco puede haber SFC (o XAND, segun la nueva nomenclatura) sin XMRV Si un determinado antirretroviral es capaz de “combatir” al XMRV debería de reflejarse en una mejora progresiva de la sintomatologia del SFC o de otras enfermedades en las que el origen tambien lo fuera. Esto seria la mejor forma de demostrar la causalidad entre XMRV y SFC. Por otro lado la capacidad mutagénica del XMRV vs el VIH se prevee mucho menor lo cual seria positivo para desarrollar una vacuna eficaz; sin embargo su baja replicación lo haría más resistente a determinados tratamientos “XMRV replicates less actively than HIV, highly active antiretroviral treatment probably is not an optimal treatment for XMRV. Its lower replication rate also may be the reason that previous attempts to link CFS to an underlying retroviral infection have been unsuccessful.” Immunoflourescence microscopy and electron microscopy of transfected 293T cells. Mice were immunized with recombinant gp70 or pr65 protein fragments, and sera were used for immunoflourescence microsocopy of 293T cells transfected two days earlier with the molecular XMRV clone VP62 or with gp70 and pr65 expression constructs. (A) A pool of sera from gp70 immunized mice showed reactivity against whole XMRV or XMRV envelope protein expressing cells. Preimmune sera showed no binding, and immune sera did not react with naive 293T cells. (B) A pool of immune sera from pr65 (Gag) immunized mice showed similar reactivity to whole virus or XMRV Gag expressing cells. Gag protein was expressed at higher levels in cells transfected with the CMV-driven codon-optimized gag construct than in those transfected with the VP62 molecular clone of XMRV. (C) Thin section of 293T cells 2 days after transfection with the VP62 molecular clone of XMRV. Particles budding at the cell membrane and a mature XMRV virion are shown. Scale bar = 100 nm. Situación ACTUAL Este descubrimiento ha aportado algo de luz sobre el desconocido SFC. El descubrimiento se publica en Science el 8 de Octubre, y algunos rotativos de gran tirada como La Vanguardia o el Pais hacen cierta mención en sus páginas interiores. Internacionalmente tambien rotativos de prestigio de USA como el New York Times, Reuters, Science New, Chicago Tribue, de UK The Times, BBC, Telegraph, The Independent, de Alemania el Bild der Wissenschaft, Spiegel o de Francia La tribune o Le Monde. Según Hillary Johnson, persona que convive con el SFC desde hace más de 20 años: “A mediados de los años 80, se empezó a hablar abiertamente del Síndrome de Fatiga Crónica. El nombre que se le puso a la enfermedad ya era un despropósito, como lo es también el rol que ha tenido la medicina ante esta enfermedad en los últimos 25 años. Ha sido una historia de difamación, marginalización, falta de eugenesia y vergüenza. Algún día los libros hablarán de los que se hizo mal y por qué se permitió que pasara esto. Escondido detrás de la bandera de la “evidencia científica” y no del sentido común ni de la justicia, a lo largo de un cuarto de siglo se ha maltratado a los enfermos del SFC y la FM o por negación, burla o con medicaciones psiquiátricas, por un grupo de médicos ineptos y con mentiras recurrentes de los responsables políticos” . Por otro lado, en un documento titulado “El XMRV: todo lo que necesitas saber hoy sobre el nuevo virus del SFC” la ligaSFC, intenta hacer llegar información de primera mano a los enfermos de SFC y FM, intenta que la desinformación total sobre este asunto llegue a la mayoría de enfermos, que respiran aliviados. Según este documento: El Síndrome de la Fatiga Crónica (SFC) es una enfermedad clasificada por la OMS con el número G 93.3.en el CIE-10. Es una enfermedad orgánica, multisistémica y crónica. Puede afectar de manera progresiva el sistema inmunológico, el neurológico, el cardiovascular y el endocrino, y se caracteriza por causar una fatiga severa, perdida sustancial de concentración y memoria, desorientación espacial, sueño no reparador, intolerancia a la luz, al sonido y a los cambios de temperatura, intolerancia al estrés emocional y a la actividad física, dolor muscular y en las articulaciones, sensibilidades químicas múltiples y una sensación de estado gripal permanente, entre otras manifestaciones. Además se han observado alteraciones severas en la función de las células NK, en la presión arterial y en el equilibrio ortostático, una notable reducción del flujo de sangre al cerebro y una reducción en la capacidad del consumo de oxígeno de las células. Al mismo tiempo, la apariencia externa del enfermo no refleja la enfermedad: su apariencia es normal. Las reacciones llevada a cabo según describe en el mismo documento las LigaSFC: Hay dos grandes agencias federales americanas que a lo largo de los últimos 25 años deberían haber liderado las investigaciones sobre el SFC, pero lamentablemente, no lo han hecho. Una de ellas, el National Institute of Health (NIH) de Washington DC, ahora, por primera vez, a través del National Cancer Insitute, se ha involucrado activamente en el tema. La otra agencia, los Centers for Disease Control de Atlanta (CDC), tiene como máximo responsable del SFC desde hace 17 años, al Dr William Reeves, que se ha caracterizado por echar abajo todos y cada uno de los estudios que podrían haber avalado el SFC como enfermedad biológica. Es también la única persona que por ahora, públicamente, ha encajado mal la noticia del descubrimiento de este nuevo retrovirus. Para empezar, ha calificado los estudios de “emocionantes pero también de muy preliminares” y ha dicho que no entiende como una revista tan prestigiosa como Science ha podido publicar un estudio en el cual “en ningún sitio dice las edades ni el sexo de los paciente evaluados, ni el tiempo que llevan enfermos o cómo enfermaron”. “Si no conozco más sobre los casos y los controles, no puedo interpretar los resultados” y añade, “Yo y otros compañeros estamos interesados en probar esta analítica con nuestros pacientes para confirmar el resultado. Si lo validamos, perfecto, aunque supongo que no será así”. (“My expectation is that we will not be able to replicate the findings”). Estas declaraciones no han extrañado a nadie, dado que el Dr Bill Reeves trabaja con enfermos que únicamente responden a los criterios del Dr Keiji Fukuda (1994) o a los criterios que él mismo promociona, los “CDC Symptom Inventory”, que nadie más utiliza, ya que se dice que es un colador de diferentes patologías, sobre todo la depresión mayor. Por suerte, otros prestigiosos laboratorios se han ofrecido para replicar el hallazgo y los resultados de los CDC pueden acabar quedando en evidencia y así acabar con la era Reeves. (El 4 de mayo del 2009, Reeves y sus colaboradores publicaron la siguiente nota: “Hay una necesidad urgente de atender los problemas psiquiátricos en la atención de los pacientes SFC”.) Si queréis saber más sobre el extraño comportamiento de los CDC, visitar la web de la periodista Hillary Johnston www.oslersweb.com Uno de los motivos que nos hace ser tan optimistas ante el descubrimiento del retrovirus XMRV es la importancia de los centros de investigación que han llevado a cabo la investigación y las personas que se han vinculado hasta ahora. No es habitual que el director del “Centre of Excellence in HIV/AIDS & Cancer Virology” del National Cancer Institut, Dr Stuart Le Grice hable del “Síndrome de la Fatiga Crónica” en los medios de comunicación y que también aproveche para recordar los primeros pasos en los descubrimientos de la epidemia del VIH, y explique en qué consiste lo que se ha descubierto. Aparte de las declaraciones del Dr Le Grice (que no es uno de los autores del estudio), tenemos las declaraciones de la Dra Sandra Rucetti que es la directora del “Retroviral Molecular Pathogenesis Section” del National Cancer Institut, hablando del descubrimiento del XMRV y del Dr Silverman, de la Cleveland Clinic, atendiendo también a la prensa. Para acabar de bordarlo, la noticia se ha publicado en la revista científica más prestigiosa, Science, y lo recoge la revista Nature. Es un gran logro para la comunidad científica que lleva tantos años investigando el SFC. Hace unas semanas aprovechando la convención anual de enfermos de SFC Norteamerica, las Autoridades Sanitarias de ese pais fueron personalmente informadas por el Dr Peterson y asesoradas por el virólogo Dr Coffin. Asimismo personal del Instituto Whittemore ha realizado diversas conferencias en Florida, California, Miami en estos últimos días y varios labotarios de referencia van a intentar validar los resultados en UK y en Australia y la semana pasada en Cleveland se reunieron a puerta cerrada más de 75 cientificos de prestigio para hablar del XMRV Colectivos de enfermos, de forma individual o a través de las asociaciones se han dirigido por cartas, e-mail, llamadas a las Autoridades Sanitarias Españolas y Autonómicas (Sra Ministra de Sanidad Trinidad Jimenez, o en Cataluña, Sra Consellera de Sanitat Marina Geli, a los Bancos de Sangre de todo el territorio nacional, a los Hospitales Provinciales de Referencia, Defensor del Pueblo, Prensa, Colegios de Médicos, Centros de Investigación, Programas de Televisión y Radio etc, etc, sin conseguir hasta la más mínima de las reacciones. Se están llevando a cabo recogida de firmas a fin de que el Gobierno informe a los afectados, a sus familias y a la población general, del peligro que podría entrañar que dicho retrovirus pasase de forma incontrolada de persona a persona, a través de la sangre o por las relaciones sexuales, y que las Autoridades Sanitarias a través de los Hospitales de Referencia de cada Provincia lleven a cabo aquellos controles para determinar la presencia del retrovirus en enfermos con “SFC” y que se establezcan de forma inmediata ensayos clínicos que conduzca a tratamientos efectivos en el menor tiempo posible. Por otro lado las Autoridades Sanitarias Americanas y de UK recomiendan que los enfermos de SFC no donen sangre hasta que se resuelva el tema, pero mientras tanto, y si se confirmase que el 3.7 % de la población asintomática es portadora del virus, los contagios de producirían a velocidad de rayo (a día de hoy con estos datos sólo en el territorio español podría haber más de 1.5 millones de personas infectadas por el XMRV). Sirva este documento, en parte científico en parte divulgativo, de percutor que haga que la clase médica se cuestione el tema del RETROVIRUS XMRV y se ponga manos a la obra para diagnosticar y tratar lo que podría ser “LA PANDEMIA QUE VIENE”. Bibliografia y referencias 1.- Detection of an Infectious Retrovirus XMRV in blood cells of Patients with Chronic Fatigue Syndrome. Lombardi, Mikovitz et al Science 8 Oct 2009 2.- Identification of a Novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q Variant RNASEL Silverman et al Plos Pathog 2006. Mar; 2 (3); e 25 3. Androgen Stimulates Transcription and Replication of XMRV (Xenotropic Murine Leukemia Virus-Related Virus). Silverman et al J Virol. 2009 Nov 11. [Epub ahead of print] 4.- Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in Chronic Fatigue Syndrome: a preliminary case series. Oytein Fluge; Olav Mella BMC Neurology 2009; 9; 28 5.- A new virus for old diseases J. M Coffin et al Science 326 (5952), 530 6.- Thyroid malignancy association with cortical and subcortical brain SPECT changes is patients presenting with a myalgic encephalomyelitis/cfs. Hyde MD, Byron et al Alasbimn Journal 10 (38) Oct 2007. Article AJ38-2 Algunos fragmentos ha sido extraidos de textos de la LigaSFC. ANEXOS 1. EL ESTUDIO DE SCIENCE REPORTS Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome Vincent C. Lombardi,1,* Francis W. Ruscetti,2,* Jaydip Das Gupta,3 Max A. Pfost,1 Kathryn S. Hagen,1 Daniel L. Peterson,1 Sandra K. Ruscetti,4 Rachel K. Bagni,5 Cari Petrow-Sadowski,6 Bert Gold,2 Michael Dean,2 Robert H. Silverman,3 Judy A. Mikovits1 , Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus–related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cellassociated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS. 1 Whittemore Peterson Institute, Reno, NV 89557, USA. 2 Laboratory of Experimental Immunology, National Cancer Institute–Frederick, Frederick, MD 21701, USA. 3 Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. 4 Laboratory of Cancer Prevention, National Cancer Institute–Frederick, Frederick, MD 21701, USA. 5 Advanced Technology Program, National Cancer Institute–Frederick, Frederick, MD 21701, USA. 6 Basic Research Program, Scientific Applications International Corporation, National Cancer Institute–Frederick, Frederick, MD 21701, USA. * These authors contributed equally to this work. To whom correspondence should be addressed. E-mail: judym{at}wpinstitute.org Chronic fatigue syndrome (CFS) is a disorder of unknown etiology that affects multiple organ systems in the body. Patients with CFS display abnormalities in immune system function, often including chronic activation of the innate immune system and a deficiency in natural killer cell activity (1, 2). A number of viruses, including ubiquitous herpesviruses and enteroviruses, have been implicated as possible environmental triggers of CFS (1). Patients with CFS often have active β herpesvirus infections, suggesting an underlying immune deficiency. The recent discovery of a gammaretrovirus, xenotropic murine leukemia virus–related virus (XMRV), in the tumor tissue of a subset of prostate cancer patients prompted us to test whether XMRV might be associated with CFS. Both of these disorders, XMRV-positive prostate cancer and CFS, have been linked to alterations in the antiviral enzyme RNase L (3–5). Using the Whittemore Peterson Institute’s (WPI’s) national tissue repository, which contains samples from well-characterized cohorts of CFS patients, we isolated nucleic acids from PBMCs and assayed the samples for XMRV gag sequences by nested polymerase chain reaction (PCR) (5, 6). Of the 101 CFS samples analyzed, 68 (67%) contained XMRV gag sequence. Detection of XMRV was confirmed in 7 of 11 WPI CFS samples at the Cleveland Clinic by PCR-amplifying and sequencing segments of XMRV env [352 nucleotides (nt)] and gag (736 nt) in CFS PBMC DNA (Fig. 1A) (6). In contrast, XMRV gag sequences were detected in 8 of 218 (3.7%) PBMC DNA specimens from healthy individuals. Of the 11 healthy control DNA samples analyzed by PCR for both env and gag, only one sample was positive for gag and none for env (Fig. 1B). In all positive cases, the XMRV gag and env sequences were more than 99% similar to those previously reported for prostate tumor–associated strains of XMRV (VP62, VP35, and VP42) (fig. S1) (5). Fig. 1. XMRV sequences in PBMC DNA from CFS patients. Single-round PCR results for gag, env, and gapdh sequences in PBMCs of (A) CFS patients and (B) healthy controls are shown. The positions of the amplicons are indicated and DNA markers (ladder) are shown. These are representative results from one group View larger version (28K): of 20 patients. [in this window] [in a new window] Sequences of full-length XMRV genomes from two CFS patients and a partial genome from a third patient were generated (table S1). CFS XMRV strains 1106 and 1178 each differed by 6 nt from the reference prostate cancer strain XMRV VP62 (EF185282 [GenBank] ), and with the exception of 1 nt, the variant nucleotides mapped to different locations within the XMRV genome, suggesting independent infections. In comparison, prostate cancer–derived XMRV strains VP35 and VP42 differed from VP62 by 13 and 10 nt, respectively. Thus, the complete XMRV genomes in these CFS patients were >99% identical in sequence to those detected in patients with prostate cancer. To exclude the possibility that we were detecting a murine leukemia virus (MLV) laboratory contaminant, we determined the phylogenetic relationship among endogenous (non-ecotropic) MLV sequences, XMRV sequences, and sequences from CFS patients 1104, 1106, and 1178 (fig. S2). XMRV sequences from the CFS patients clustered with the XMRV sequences from prostate cancer cases and formed a branch distinct from non-ecotropic MLVs common in inbred mouse strains. Thus, the virus detected in the CFS patients’ blood samples is unlikely to be a contaminant. To determine whether XMRV proteins were expressed in PBMCs from CFS patients, we developed intracellular flow cytometry (IFC) and Western blot assays, using antibodies (Abs) with novel viral specificities. These antibodies included, among others, (i) rat monoclonal antibody (mAb) to the spleen focus-forming virus (SFFV) envelope (Env), which reacts with all polytropic and xenotropic MLVs (7); (ii) goat antisera to whole mouse NZB xenotropic MLV; and (iii) a rat mAb to MLV p30 Gag (8). All of these Abs detected the human VP62 XMRV strain grown in human Raji, LNCaP, and Sup-T1 cells (fig. S3) (5). IFC of activated lymphocytes (6, 9) revealed that 19 of 30 PBMC samples from CFS patients reacted with the mAb to MLV p30 Gag (Fig. 2A). The majority of the 19 positive samples also reacted with antisera to other purified MLV proteins (fig. S4A). In contrast, 16 healthy control PBMC cultures tested negative (Fig. 2A and fig. S4A). These results were confirmed by Western blots (Fig. 2, B and C) (6) using Abs to SFFV Env, mouse xenotropic MLV, and MLV p30 Gag. Samples from five healthy donors exhibited no expression of XMRV proteins (Fig. 2C). The frequencies of CFS cases versus healthy controls that were positive and negative for XMRV sequences were used to calculate a Pearson 2 value of 154 (two-tailed P value of 8.1 x 10–35). These data yield an odds ratio of 54.1 (a 95% confidence interval of 23.8 to 122), suggesting a nonrandom association with XMRV and CFS patients. Fig. 2. Expression of XMRV proteins in PBMCs from CFS patients. (A) PBMCs were activated with phytohemagglutinin and interleukin-2, reacted with a mAb to MLV p30 Gag, and analyzed by IFC. (B) Lysates of activated PBMCs from CFS patients (lanes 1 to 5) were analyzed by Western blots with rat mAb to SFFV Env (top panel), goat antiserum to xenotropic MLV (middle panel), or goat antiserum to MLV p30 Gag View larger version (63K): (bottom panel). Lane 7, lysate from SFFV-infected HCD57 cells. Molecular weight markers in kilodaltons are at [in this window] left. (C) Lysates of activated PBMCs from healthy donors [in a new window] (lanes 1, 2, 4, 5, and 7) or from CFS patients (lanes 3 and 6) were analyzed by Western blots using rat mAb to SFFV Env (top panel) or goat antiserum to MLV p30 Gag (bottom panel). Lane 8, SFFV-infected HCD-57 cells. Molecular weight (MW) markers in kilodaltons are at left. (D) CD4+ T cells (left) or CD19+ B cells (right) were purified, activated, and examined by flow cytometry for XMRV Gag with a mAb to MLV p30 Gag. To determine which types of lymphocytes in blood express XMRV, we isolated B and T cells from one patient’s PBMCs (6). Using mAb to MLV p30 Gag and IFC, we found that both activated T and B cells were infected with XMRV (Fig. 2D and fig. S4A). Furthermore, using mAb to SFFV Env, we found that >95% of the cells in a B cell line developed from another patient were positive for XMRV Env (fig. S4B). XMRV protein expression in CFS patient–derived activated T and B cells grown for 42 days in culture was confirmed by Western blots (fig. S4C) using Abs to SFFV Env and xenotropic MLV. We next investigated whether the viral proteins detected in PBMCs from CFS patients represent infectious XMRV. Activated lymphocytes (6) were cocultured with LNCaP, a prostate cancer cell line with defects in both the JAK-STAT and RNase L pathways (10, 11) that was previously shown to be permissive for XMRV infection (12). After coculture with activated PBMCs from CFS patients, LNCaP cells expressed XMRV Env and multiple XMRV Gag proteins when analyzed by Western blot (Fig. 3A) and IFC (fig. S5A). Transmission electron microscopy (EM) of the infected LNCaP cells (Fig. 3B), as well as virus preparations from these cells (Fig. 3C), revealed 90- to 100-nm-diameter budding particles consistent with a gamma (type C) retrovirus (13). Fig. 3. Infectious XMRV in PBMCs from CFS patients. (A) Lysates of LNCaP cells cocultured with PBMCs from CFS patients (lanes 1, 3, and 5) or healthy donors (lanes 2 and 4) were analyzed by Western blots with rat mAb to View larger version (43K): SFFV Env (top panel) or goat antiserum to xenotropic [in this window] MLV (bottom panel). Lane 6, uninfected LNCaP; lane 7, [in a new window] SFFV-infected HCD-57 cells. MW markers in kilodaltons are at left. (B) Transmission electron micrograph of a budding viral particle from LNCaP cells infected by incubation with an activated T cell culture from a CFS patient. (C) Transmission electron micrograph of virus particles released by infected LNCaP cells. We also found that XMRV could be transmitted from CFS patient plasma to LNCaP cells when we applied a virus centrifugation protocol to enhance infectivity (6, 14, 15). Both XMRV gp70 Env and p30 Gag were abundantly expressed in LNCaP cells incubated with plasma samples from 10 of 12 CFS patients, whereas no viral protein expression was detected in LNCaP cells incubated with plasma samples from 12 healthy donors (Fig. 4A). Likewise, LNCaP cells incubated with patient plasma tested positive for XMRV p30 Gag in IFC assays (fig. S5B). We also observed cell-free transmission of XMRV from the PBMCs of CFS patients to the T cell line SupT1 (Fig. 4B) and both primary and secondary transmission of cell-free virus from the activated T cells of CFS patients to normal T cell cultures (Fig. 4C). Together, these results suggest that both cell-associated and cell-free transmission of CFS-associated XMRV are possible. Fig. 4. Infectious XMRV and antibodies to XMRV in CFS patient plasma. (A) Plasma from CFS patients (lanes 1 to 6) were incubated with LNCaP cells and lysates were prepared after six passages. Viral protein expression was detected by Western blots with rat mAb to SFFV Env (top panel) or goat antiserum to MLV p30 Gag (bottom panel). Lane 7, uninfected LNCaP; lane 8, SFFV-infected HCDView larger version (43K): 57 cells. MW markers in kilodaltons are at left. (B) Cell[in this window] free transmission of XMRV to the SupT1 cell line was [in a new window] demonstrated using transwell coculture with patient PBMCs, followed by nested gag PCR. Lane 1, MW marker. Lane 2, SupT1 cocultured with Raji. Lanes 3 to 7, SupT1 cocultured with CFS patient PBMCs. Lane 8, no template control (NTC). (C) Normal T cells were exposed to cell-free supernatants obtained from T cells (lanes 1, 5, and 6) or B cells (lane 4) from CFS patients. Lanes 7 and 8 are secondary infections of normal activated T cells. Initially, uninfected primary T cells were exposed to supernatants from PBMCs of patients WPI1220 (lane 7) and WPI-1221 (lane 8). Lanes 2 and 3, uninfected T cells; lane 9, SFFV-infected HCD-57 cells. Viral protein expression was detected by Western blot with a rat mAb to SFFV Env. MW markers in kilodaltons are at left. (D) Plasma samples from a CFS patient or from a healthy control as well as SFFV Env mAb or control were reacted with BaF3ER cells (top) or BaF3ER cells expressing recombinant SFFV Env (bottom) and analyzed by flow cytometry. IgG, immunoglobulin G. We next investigated whether XMRV stimulates an immune response in CFS patients. For this purpose, we developed a flow cytometry assay that allowed us to detect Abs to XMRV Env by exploiting its close homology to SFFV Env (16). Plasma from 9 out of 18 CFS patients infected with XMRV reacted with a mouse B cell line expressing recombinant SFFV Env (BaF3ER-SFFV-Env) but not to SFFV Env negative control cells (BaF3ER), analogous to the binding of the SFFV Env mAb to these cells (Fig. 4D and S6A). In contrast, plasma from seven healthy donors did not react (Fig. 4D and fig. S6A). Furthermore, all nine positive plasma samples from CFS patients but none of the plasma samples from healthy donors blocked the binding of the SFFV Env mAb to SFFV Env on the cell surface (fig. S6B). These results are consistent with the hypothesis that CFS patients mount a specific immune response to XMRV. Neurological maladies and immune dysfunction with inflammatory cytokine and chemokine up-regulation are some of the most commonly reported features associated with CFS. Several retroviruses, including the MLVs and the primate retroviruses HIV and HTLV-1, are associated with neurological diseases as well as cancer (17). Studies of retrovirusinduced neurodegeneration in rodent models have indicated that vascular and inflammatory changes mediated by cytokines and chemokines precede the neurological pathology (18, 19). The presence of infectious XMRV in lymphocytes may account for some of these observations of altered immune responsiveness and neurological function in CFS patients. We have discovered a highly significant association between the XMRV retrovirus and CFS. This observation raises several important questions. Is XMRV infection a causal factor in the pathogenesis of CFS or a passenger virus in the immunosuppressed CFS patient population? What is the relationship between XMRV infection status and the presence or absence of other viruses that are often associated with CFS (e.g., herpesviruses)? Conceivably these viruses could be cofactors in pathogenesis, as is the case for HIV-mediated disease, in which co-infecting pathogens play an important role (20). Patients with CFS have an elevated incidence of cancer (21). Does XMRV infection alter the risk of cancer development in CFS? As noted above, XMRV has been detected in prostate tumors from patients expressing a specific genetic variant of the RNASEL gene (5). In contrast, in our study of this CFS cohort, we found that XMRV infection status does not correlate with the RNASEL genotype (6) (table S2). Finally, it is worth noting that 3.7% of the healthy donors in our study tested positive for XMRV sequences. This suggests that several million Americans may be infected with a retrovirus of as yet unknown pathogenic potential. Supporting Online Material www.sciencemag.org/cgi/content/full/1179052/DC1 Materials and Methods Figs. S1 to S6 Tables S1 and S2 References References and Notes 1. L. D. Devanur, J. R. Kerr, J. Clin. Virol. 37, 139 (2006). [CrossRef] [Web of Science] [Medline] 2. T. L. Whiteside, D. Friberg, Am. J. Med. 105, 27S (1998). [Medline] 3. R. J. Suhadolnik et al., J. Interferon Cytokine Res. 17, 377 (1997). [Web of Science] [Medline] 4. G. Casey et al., Nat. Genet. 32, 581 (2002). [CrossRef] [Medline] 5. A. Urisman et al., PLoS Pathog. 2, e25 (2006). [CrossRef] [Medline] 6. Materials and methods are available as supporting material on Science Online. 7. R. Wolff, S. Koller, J. Ruscetti, Virology 43, 472 (1982). 8. B. Chesebro et al., Virology 127, 134 (1983). [CrossRef] [Web of Science] [Medline] 9. K. A. Smith, F. W. Ruscetti, Adv. Immunol. 31, 137 (1981). [Web of Science] [Medline] 10. G. Dunn, K. Sheehan, L. Old, R. Schreiber, Cancer Res. 65, 3447 (2005).[Abstract/Free Full Text] 11. Y. Xiang et al., Cancer Res. 63, 6795 (2003).[Abstract/Free Full Text] 12. B. Dong et al., Proc. Natl. Acad. Sci. U.S.A. 104, 1655 (2007). [Abstract/Free Full Text] 13. B. J. Poiesz et al., Proc. Natl. Acad. Sci. U.S.A. 77, 7415 (1980). [Abstract/Free Full Text] 14. G. R. Pietroboni, G. B. Harnett, M. R. Bucens, J. Virol. Methods 24, 85 (1989). [CrossRef] [Web of Science] [Medline] 15. S. M. Yoo et al., J. Virol. Methods 154, 160 (2008). [CrossRef] [Web of Science] [Medline] 16. L. Wolff, E. Scolnick, S. Ruscetti, Proc. Natl. Acad. Sci. U.S.A. 80, 4718 (1983). [Abstract/Free Full Text] 17. C. Power, Trends Neurosci. 24, 162 (2001). [CrossRef] [Web of Science] [Medline] 18. X. Li, C. Hanson, J. Cmarik, S. Ruscetti, J. Virol. 83, 4912 (2009). [Abstract/Free Full Text] 19. K. E. Peterson, B. Chesebro, Curr. Top. Microbiol. Immunol. 303, 67 (2006). [Web of Science] [Medline] 20. A. Lisco, C. Vanpouille, L. Margolis, Curr. HIV/AIDS Rep. 6, 5 (2009). [CrossRef] [Medline] 21. P. H. Levine et al., Cancer Res. 52, 5516s (1992).[Abstract/Free Full Text] 22. We thank D. Bertolette, Y. Huang, C. Hanson, and J. Troxler for technical assistance; K. Nagashima for EM; and C. Ware and K. Hunter for discussions. Funded by the Whittemore Peterson Institute and the Whittemore Family Foundation; the National Cancer Institute (NCI); NIH (under contract HHSN26120080001E); and grants to R.H.S. from NCI/NIH (CA104943), the U.S. DoD Prostate Cancer Research Program (W81XWH07-1338), the V Foundation for Cancer Research, the Charlotte Geyer Foundation, and Mal and Lea Bank. The content of this publication does not reflect the views or policies of the U.S. DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. R.H.S. may receive royalty payments in the future from Abbott Laboratories. GenBank accession numbers are as follows: WPI-1130, GQ483508 [GenBank] ; WPI-1138, GQ483509 [GenBank] ; WPI-1169, GQ483510 [GenBank] ; WPI-1178, GQ497343; WPI-1106, GQ497344; and WPI-1104, GQ497345. Note added in proof: V.C.L. is operations manager of Viral Immune Pathologies Laboratory, which is in negotiations with the Whittemore Peterson Institute to offer a dianostic test for XMRV. Received for publication 14 July 2009. Accepted for publication 31 August 2009 POR TU SEGURIDAD: UN TEST DIAGNOSTICO DEL RETROVIRUS XMRV View Current Signatures - Sign the Petition To: MINISTERIO DE SANIDAD POR LA SEGURIDAD EN LOS BANCOS DE SANGRE Y UNA CAMPAÑA DE INFORMACION SOBRE EL RETROVIRUS ONCOGENO XMRV PRESENTE EN 2.000.000 DE ESPAÑOLES!! LEE ESTA CARTA Y FIRMALA POR LA SEGURIDAD DE TODOS Y LA INVESTIGACION PARA TRATAMIENTOS DE LOS AFECTADOS POR ESTE NUEVO RETROVIRUS. Estimada Trinidad Jiménez (Ministra de Sanidad) y José Luis Rodríguez Zapatero (Presidente del Gobierno): Le escribo estas líneas para informarle del que posiblemente sea el descubrimiento medico mas importante en una década. El pasado 8 de octubre, la revista Science publicó un artículo que relaciona un retrovirus llamado XMRV con el Síndrome de Fatiga Crónica (SFC). Previamente este retrovirus también había sido vinculado al cáncer de próstata. Los científicos del Whittemore Peterson Institute (WPI) en Reno, Nevada, la Clínica de Cleveland y el Instituto Nacional del Cáncer de los EEUU, detectaron el ADN del retrovirus XMRV en las células sanguíneas de 68 de 101 pacientes (67%) de Síndrome de Fatiga Crónica, en comparación con 8 de los 218 controles sanos (3,7 %). En este primer estudio, buscaron el ADN solo en el núcleo de la célula, pero en pruebas posteriores, buscando también en el plasma, el porcentaje subió al 98% en las personas con Síndrome de Fatiga Crónica, sin que hubiera modificación en los controles sanos. De esta forma comprobaron que el XMRV está prácticamente en todos los pacientes de SFC. El hecho de que este retrovirus se encuentre en casi todos los afectados del SFC hace pensar que su rol es muy importante y determinante. Siguientes estudios tendrán que determinar (entre otros aspectos) si el XMRV es el causante que provoca el desarreglo inmunológico del SFC o si se aprovecha de un desarreglo en el sistema inmunológico para atacar. Los científicos siguen trabajando para tener un control más preciso del retrovirus y conseguir una prueba simple que pueda mostrar si tienes el XMRV de forma activa o no, algo que piensan saldrá pronto. EL XMRV ES UN RETROVIRUS. Esto quiere decir que tiene la capacidad de ocultar su código genético integrándolo en el de las células que infecta. Una característica de este retrovirus que ha llamado la atención a los científicos, es que los XMRV encontrados en los pacientes del SFC son genéticamente idénticos, aún cuando provengan de zonas geográficas alejadas. Esto hace pensar que se trata de un virus bastante reciente (en términos biológicos), primitivo y poco evolucionado y, esperan que su capacidad de replicación sea relativamente baja. Cada vez que un retrovirus se reproduce, rehace su genoma, y por eso la posibilidad de pequeños cambios o alteraciones genéticas son muy comunes. El hecho de que estos virus sean tan similares, es en sí, extraño. El XMRV ES UN GAMMARETROVIRUS relacionado con la leucemia en ratas y fue identificado por primera vez en humanos en 2007 por el doctor Robert Silverman, del departamento de Biología de Cáncer de la Clínica Cleveland, EEUU, trabajando en tejidos de cáncer de próstata. El XMRV sería el tercer retrovirus PATÓGENO encontrado en la especie humana. Sólo hay otros dos retrovirus conocidos en el ser humano: la Leucemia de células T y el VIH. Los retrovirus están asociados con deficiencias inmunológicas, enfermedades inflamatorias, enfermedades neurológicas y el cáncer. Este virus también esta presente en una gran cantidad de enfermedades neuroinmunes, incluido el autismo y la fibromialgia. EL SÍNDROME DE FATIGA CRÓNICA (SFC), (mal llamado fatiga crónica) es una enfermedad debilitante de etiología desconocida. Se estima que afecta a 17 millones de personas en todo el mundo (entre los países desarrollados). Está clasificada por la Organización de la Salud con el número G93.3 en el CIE-10. Es una enfermedad orgánica, multisistémica y crónica. Afecta de manera progresiva el sistema inmunológico, el neurológico, el cardiovascular y el endocrino, y se caracteriza por causar una fatiga severa, pérdida sustancial de concentración y memoria, desorientación espacial, sueño no reparador, intolerancia a la luz, al sonido y a los cambios de temperatura, intolerancia al estrés emocional y a la actividad física, dolor muscular y articular, sensibilidades a químicos y una sensación de estado gripal permanente, entre otras manifestaciones. Además se han observado alteraciones severas en la función de las células NK, en la presión arterial y en el equilibrio ortostático, una notable reducción del flujo de sangre al cerebro y una reducción en la capacidad del consumo de oxígeno de las células. Al mismo tiempo, la apariencia externa del enfermo no refleja la enfermedad: su apariencia es normal. A pesar del reconocimiento del SFC como enfermedad orgánica por parte de los expertos e incluso por la Organización Mundial de la Salud y estudios que mostraban, la inmunodeficiencia entre las células NK, y subgrupos linfocitarios, ratio Th1/Th2, los médicos no expertos en la enfermedad, (que son la gran mayoría) la han catalogado como una enfermedad mental, inexistente. Las personas con Síndrome de Fatiga Crónica han sido derivadas a salud mental considerando a los enfermos desde mentirosos, farsantes y vagos, hasta depresivos. Esto ha supuesto para los enfermos, que durante años están sin diagnóstico correcto, ver como sus capacidades físicas e intelectuales se van mermando sin que nadie les explique, ni siquiera, que les está pasando. Esta postura médica ha influido tanto en el ámbito social, administrativo y familiar del enfermo que le ha llevado a un forzado aislamiento social y familiar. Ahora encuentran un retrovirus que puede explicar la sintomatología de una enfermedad tan compleja como el Síndrome de Fatiga Crónica y que, tanto si es causa directa como si es indirecta, deja latente que la salud de los enfermos de SFC está muy deteriorada: deficiencia inmunológica, alteraciones neurológicas, endocrinas… El estudio ha tenido repercusión a nivel mundial: EEUU, Japón, Reino Unido, Bélgica, Cuba,.. realizan las investigaciones pertinentes para tomar las medidas necesarias. En España esta información parece haber pasado de refilón, sólo se ha publicado una pequeña nota en La Vanguardia y en El País, y no ha salido en ninguna televisión o radio. Mientras tanto a nivel internaciona 75 de los más prestigiosos científicos están reunidos en Cleveland para determinar el mecanismo patógeno del retrovirus, clarificar las vás de transmisión, estudiar posibles tratamientos y vacuna. España no esta presente en esta cumbre. http://www.cleveland.com/healthfit/index.ssf/2009/11/top_scientists_to_meet_at_clev.html Lo deseable sería que el Ministerio de Sanidad se informe correctamente e inicie algún protocolo de atención a los enfermos potencialmente portadores del retrovirus (especialmente los que padecen SFC). No es aceptable la sobredimensión que se le esta dando al virus de la gripe A, que contrasta con la práctica negación de este nuevo retrovirus XMRV vinculado al cáncer de próstata y enfermedades neuroinmunológicas como el SFC y el Autismo. Hay que tener presente que un 3,7% de la población es portadora de un retrovirus potencialmente patógeno y aun no se conocen sus vías de transmisión, dejando patente el riesgo público a priori para los bancos de sangre. Es responsabilidad del Gobierno y del Ministerio de sanidad tomar parte en la información a la sociedad, colaboración en los estudios que se están coordinando a nivel internacional y la prevención a la hora de donar o tomar sangre que no este contaminada con XMRV. Es también la responsabilidad del Ministerio de Sanidad informar al colectivo medico del vinculo existente entre este retrovirus XMRV y el Síndrome de Fatiga Crónica y el Cáncer de Próstata. No sería aceptable después de este hallazgo medico que algunos médicos ignorantes sigan recetando terapia cognitiva conductual o antidepresivos a los pacientes de SFC, pues esto solo aumentara el daño mitocondrial y reduce las defensas de un sistema inmunológico ya deprimido por un retrovirus. Espero que sí tengan en cuenta esta información, y tomen las medidas necesarias que eviten reproches de la sociedad en general y de sus votantes en particular en cuanto a su gestión a la hora de tomar acciones como si se esta haciendo a nivel internacional. Atentamente, TU NOMBRE Y APELLIDOS Y DNI Sincerely, The Undersigned Click Here to Sign Petition Chronic fatigue syndrome, cancer linked to new virus Share: By CZERNE REID Published: November 3rd, 2009 • Category: Medicine, Staff Judy Mikovits, Ph.D. A newly identified virus has been found to be linked to chronic fatigue syndrome and might also provide clues about how to prevent prostate cancer, according to a report this month in the journal Science. Called XMRV, the virus is transmitted in blood and body fluids and might be a significant public health threat. Judy Mikovits, Ph.D., senior author of the paper, described the research during grand rounds at the University of Florida College of Medicine Thursday, Oct. 20. She was a guest of the division of hematology/oncology. “This discovery opens a new area of medical possibilities for people who have a condition that has baffled doctors and researchers for years, and gives an insight into potential prevention and cures of cancer.” Chronic fatigue syndrome is a multi-system disorder that is the subject of much controversy surrounding whether it is a true medical condition. Its cause is unknown and there are no diagnostic tests. It affects an estimated 17 million people worldwide. Mikovits, who is research director at the Whittemore Peterson Institute in Nevada, and colleagues, found that 67 percent of 101 patients who had chronic fatigue syndrome also had the virus. In contrast, the virus was present in about 4 percent of 218 controls who did not have the syndrome. XMRV, short for xenotropic murine leukemia virus-related virus, affects the immune system. It exists in blood and body fluids and is readily transmitted. Chronic fatigue syndrome sufferers’ relatives who had been diagnosed with neuroimmune diseases such as atypical multiple sclerosis, fibromyalgia and autism also tested positive for the virus, though these data were obtained after the publication and are still preliminary. Sequences of the virus had previously been found in men who have prostate cancer. Mikovits also showed preliminary data that CFS patients in the study who subsequently developed cancer, primarily lymphoma, all tested positive for the XMRV. That raises the possibility that treating the virus could ultimately prevent many cancers, she said. “It opens a new path for understanding the pathogenesis of cancer,” said Carmen Allegra, M.D., chief of hematology/oncology at UF College of Medicine. Researchers say the level of XMRV infection revealed in the study is not just a concern among people who have chronic fatigue syndrome, but is a public health issue as well. “This is the discovery of a new virus that doesn’t have any treatment, affects 4 percent of the population and has a transmission that seems to be easy,” Allegra said. Researchers continue to seek answers to many unanswered questions about the virus, including how it got into the human population, how it acts to cause disease and whether the virus alters the risk of cancer development in people who have chronic fatigue syndrome. “There’s quite a bit of work to do to understand the risk associated with this,” said Nam Dang, M.D., Ph.D., deputy chief of hematology/oncology. Tagged as: Carmen Allegra, Judy Mikovits, Nam Dang, XMRV SOBRE CITOQUINAS White’s assertion that immune or viral measures are not involved in the maintenance of the disorder would seem to be a direct denial of the evidence of two of the world’s leading immunologists who specialise in ME/CFS, Professors Mary Ann Fletcher and Nancy Klimas, who recently published yet more confirmatory evidence of immune dysfunction in the maintenance of the disorder (Journal of Translational Medicine 2009:7:96: doi:10.1186/1479-5876-7-96). Their peer reviewed article was published immediately upon acceptance. Fletcher and Klimas et al are clear that cytokine abnormalities are common in (ME)CFS and that the cytokine changes observed are more likely to be indicative of immune activation and inflammation, rather than specific for (ME)CFS, as people with fibromyalgia, Gulf War Illness, rheumatological disorders and multiple sclerosis may also have similar cytokine patterns. The authors do, however, demonstrate that several of the abnormal cytokines show promise as potential biomarkers for (ME)CFS. As Fletcher and Klimas et al point out: “CFS studies from our laboratory and others have described cytokine abnormalities. Other studies reported no difference between (ME)CFS and controls. However, methodologies varied widely and few studies measured more than 4 or 5 cytokines. Multiplex technology permits the determination of cytokines for a large panel of cytokines simultaneously with high sensitivity. “In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers. However, the cytokine changes observed are likely to be more indicative of immune activation and inflammation…Many of the symptoms are inflammatory in nature. “There is a considerable literature describing immune dysfunction in (ME)CFS. “The goal of this study was to determine if, using new technology, plasma cytokines had sufficient sensitivity and specificity to distinguish (ME)CFS cases from age-matched healthy controls….Amounts of cytokines in plasma or serum are often below the level of detection in traditional ELISA assays. “The availability of sensitive multiplex technology permitted the determination of 16 cytokines simultaneously…In the (ME)CFS cases, we found an unusual pattern of the cytokines that define the CD4 T cell. “Pro-inflammatory cytokines: A significant elevation in the relative amounts of 4 of 5 proinflammatory cytokines in peripheral blood plasma of patients with (ME)CFS was found when compared with the controls. In cases, lymphotoxin (LT) was elevated by 257% and IL-6 by 100% over the controls. “TH2 cytokines: Both interleukin (IL)-4 and IL-5 were elevated in (ME)CFS, with the median of IL-4 (being) 240% and of IL-5 (being) 95% higher in cases than controls. “Anti-inflammatory cytokines: IL-3 was significantly lower in (ME)CFS patients. “TH1 cytokines: IL-12 was significantly elevated (120%) and IL-15 decreased (15%) in cases compared to controls. “IL-8 (CXCL8): this chemokine was 42% lower in the (ME)CFS patients. “Along with the TH1 abnormalities, we found up-regulation of TH2 associated cytokines, IL-4 and IL5, in the (ME)CFS subjects. Allergy is common in (ME)CFS cases. Years ago, Straus et al reported >50% atopy in 24 CFS patients. “The probability of chronic inflammation in (ME)CFS patients is supported by the elevation of four members of the pro-inflammatory cytokine cascade , LT, IL-1, IL-1 and IL-6, in the (ME)CFS samples compared to controls. “Interleukin-13, associated with inhibitory effects on inflammatory cytokine production, was lower in cases compared to controls. “The inflammatory mediator IL-8 (a chemokine known as CXCL8) known to be responsible for migration and activation of neutrophils and NK cells was decreased in plasma of (ME)CFS patients. “The observations of abnormal cytokine patterns in (ME)CFS patients support the reports of retrovirus infections. “Recently, DNA from a human gammaretrovirus, xenotropic murine leukaemia virus-related virus (XMRV) was found in the PBMC of 68 of 101 patients compared to 8 of 218 healthy controls. Patient–derived, activated PBMC produced infectious XMRV in vitro. Both cell associated and cell-free transmission of the virus to uninfected primary lymphocytes and indicator cell lines was possible. “The decreased natural killer (NK) cell cytotoxic and lymphoproliferative activities and increased allergic and autoimmune manifestations in (ME)CFS would be compatible with the hypothesis that the immune system of affected individuals is biased towards a T-helper (TH) 2 type, or humoral immunity-orientated cytokine pattern. “The elevations in LT, IL-1, IL1 and IL-6 indicate inflammation, likely to be accompanied by autoantibody production, inappropriate fatigue, myalgia and arthralgia, as well as changes in mood and sleep patterns. “This study is among the first in the (ME)CFS literature to report the plasma profiles of a reasonably large panel of cytokines assessed simultaneously by multiplex technique. “Cytokine abnormalities appear to be common in (ME)CFS. The changes from the normal position indicate immune activation and inflammation. “The results imply a disorganised regulatory pattern of TH1 function, critical to antiviral defence. “The results from this study support a TH2 shift, pro-inflammatory cytokine up-regulation and downregulation of important mediators of cytotoxic cell function”. Since it is now unequivocal that people with (ME)CFS show markers of inflammation, what will be the impact on the Wessely School’s MRC PACE Trial that is predicated on the assumptions of deconditioning, on the “perception” of effort and on aberrant illness beliefs and whose participants are instructed about “sleep hygiene”? Plasma cytokines in women with chronic fatigue syndrome Chronic Fatigue Syndrome (CFS) studies from our laboratory and others have described cytokine abnormalities. Other studies reported no difference between CFS and controls. However, methodologies varied widely and few studies measured more than 4 or 5 cytokines. Multiplex technology permits the determination of cytokines for a large panel of cytokines simultaneously with high sensitivity and with only 30ul of plasma per sample. No widely accepted laboratory test or marker is available for the diagnosis or prognosis of CFS. This study screened plasma factors to identify circulating biomarkers associated with CFS. Methods: Cytokines were measured in plasma from female CFS cases and healthy controls. Multiplex technology provided profiles of 16 plasma factors including the pro -inflammatory cytokines: tumor necrosis factor alpha (TNFalpha), lymphotoxin alpha (LTalpha), interleukin (IL) - IL-Ialpha, IL-1beta, IL-6; TH1 cytokines: interferon gamma (IFNgamma), IL-12p70, IL-2, IL-15; TH2: IL-4, IL-5; TH17 cytokines, IL-17 and IL-23; anti-inflammatory cytokines IL-10, IL13; the inflammatory mediator and neutrophil attracting chemokine IL-8 ( CXCL8). Analysis by receiver operating characteristic (ROC) curve assessed the biomarker potential of each cytokine. Results: The following cytokines were elevated in CFS compared to controls: LTalpha, IL-1alpha, IL-1beta, IL-4, IL-5, IL-6 and IL-12. The following cytokines were decreased in CFS: IL-8, IL-13 and IL-15. The following cytokines were not different: TNFalpha, IFNgamma, IL-2,IL-10, IL-23 and IL-17. Applying (ROC) curve analyses, areas under the curves (AUC) for IL-5 (0. 84), LTalpha (0.77), IL-4 (0.77), IL-12 (0.76) indicated good biomarker potential. The AUC of IL-6 (0.73), IL-15 (0.73), IL-8 (0.69), IL-13 (0.68) IL-1alpha (0.62), IL-1beta (0.62) showed fair potential as biomarkers. Conclusions: Cytokine abnormalities are common in CFS. In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers. However, the cytokine changes observed are likely to more indicative of immune activation and inflammation, rather than specific for CFS. As such, they are targets for 3 therapeutic strategies. Newer techniques allow evaluation of large panels of cytokines in a cost effective fashion. Author: Mary FletcherXiao ZengZachary BarnesSilvina LevisNancy Klimas Credits/Source: Journal of Translational Medicine 2009, 7:96 AUTISMO Y XMRV PUBLICADO EN THE HUFFINGTON POS 17 NOV 2009 Last week, researchers from the University of Nevada, the National Cancer Institute and The Cleveland Clinic announced the startling discovery of antibodies to a little known retrovirus in 95% of patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating neuro-immune disease impacting more than a million people in the United States. The finding, published in the highly respected journal Science, "clearly points to the retrovirus as a significant contributing factor in this illness," said lead author Judy Mikovits, Ph.D., director of research for the Whittemore Peterson Institute for Neuro-Immune Disease, which is affiliated with the University of Nevada, Reno. It was the first study to isolate particles of the retrovirus, XMRV, in human blood and demonstrate that it is transmitted between blood cells. XMRV was first discovered in prostate cancer tissue of men with certain genetic defects. Like the more well-known retrovirus, HIV, this pathogen is blood-borne, and not transmitted through the air. The findings have potential significance for a number of other disorders including, it turns out, autism. Researchers tested blood samples from a "small group of children" with autism and found that 40% of them were positive for XMRV, according to a statement from the Nevada Commission on Autism Spectrum Disorders. More testing is underway which, the Commission said, "could dramatically increase that 40% positive finding." (Given the small sample size, such a statement is purely speculative). As Dr. Mikovits explained to a television news program in Nevada, "It is not in the paper and not reported, but we have actually done some of these studies (in ASD children) and found the virus in a significant number of samples that we have tested for. It could be linked to a number of neuroimmune diseases, including autism. It certainly won't be all, because there are genetic defects that result in autism. But there are also the environmental effects; there is always the hypothesis that, 'My child was fine and then they got sick, and then they got autism.'" According to Dr. Mikovits, XMRV (which admittedly sounds like a satellite radio system for your Winnebago) can lie dormant in people, until it is "turned on or off" by other factors, such as stress hormones like cortisol, or in response to the presence of inflammatory "cytokines," protein molecules secreted by immune cells to help regulate the immune system. And then Dr. Mikovits dropped a bombshell that is sure to spark controversy. "On that note, if I might speculate a little bit," she said, "This might even explain why vaccines would lead to autism in some children, because these viruses live and divide and grow in lymphocytes -- the immune response cells, the B and the T cells. So when you give a vaccine, you send your B and T cells in your immune system into overdrive. That's its job. Well, if you are harboring one virus, and you replicate it a whole bunch, you've now broken the balance between the immune response and the virus. So you have had the underlying virus, and then amplified it with that vaccine, and then set off the disease, such that your immune system could no longer control other infections, and created an immune deficiency." So there you have it - a possible explanation of regressive autism in a significant number of cases associated with immune system deregulation triggered by vaccination. Of course, much more work is needed to nail down the exact significance of such an association. For example, is the virus implicated in the cause of autism, or do children harbor the virus as a result of autism? Either way, it is notable that such questions are being asked by mainstream sources such as the University of Nevada, and by extension the NCI and the Cleveland Clinic: Can XMRV infection plus vaccination create the right conditions for regressive autism? That remains to be seen. But it also means that the thousands of parents who claim their children did regress shortly after vaccination may not be so crazy and "fringe" as they have been portrayed by experts such as Dr. Paul Offit of Children's Hospital of Philadelphia and Dr. Thomas Insel, head of the National Institute of Mental Health and Chair of the federal Interagency Autism Coordinating Committee (IACC). "We certainly are advocating vaccinations and how important those are to the well being of the children," explained Annette Whittemore, founder of the Whittemore Peterson Institute. "But what we are hoping for is, by finding out whether or not one is positive to XMRV, whether it is in one family member or another, and then looking for it in children, you could alter the immune response in such a way that you can protect the child and still be able to vaccinate and avoid autism in these kids. And again, I don't think ether one of us is sitting here saying, 'Vaccinations cause autism,' but rather a number of factors; a genetic susceptibility to the illness, to the infection itself, and then on top of that you are adding something to that mix that takes that child over the top." Apparently, the CFS findings have impressed the scientific community. "We presented these data three times: Twice at closed conferences at the NIH, and one at an international meeting a few weeks ago, and you could hear a pin drop in the audience - it's amazement" Mikovits said. "The scientists are excited, everyone is working on it, so we know we are going to get a lot of help. It's just amazement, it's an entirely new field of medicine and everyone who's ever worked in this family of viruses is, now that we've shown it's a human pathogen, is extremely excited." Whittemore added that researchers hoped to develop a vaccine against XMRV quickly, noting that "It would be easier to find a vaccine against this than HIV, because it is a simple retrovirus." The discovery raises more questions than it answers. What, exactly, is it about immunization that might switch on XMRV viral expression? Could the effect of heavy metals upon cytokine balances be at play? Where did this retrovirus come from, and how did it apparently become so prevalent in children with autism? Did these children inherit the virus from a parent, or was there some other unexplained route of transmission? Why has the NIH said nothing about XMRV in association with autism, and did Dr. Insel know about these findings without sharing them with the IACC? Finally, Dr. Insel has said that a vaccine against autism may one day be developed. Was he actually referring to a vaccine against XMRV, and what role, if any, might he or members of his family play in the development of such a vaccine? According to Insel's own biography, in 1994, he went to Emory University, Atlanta as a Professor in the Department of Psychiatry, and Director of the Yerkes Regional Primate Research Center. "As director of Yerkes," his bio says, "Dr. Insel built one of the nation's leading HIV vaccine research programs." ENTREVISTA A COFFIN (RETROVIROLOGO) SOBRE EL XMRV October 16, 2009 Scientists have identified a virus lurking in 68 of 101 patients diagnosed with chronic fatigue syndrome. Whether the virus — known as XMRV — causes the syndrome is unclear. Molecular biologist John Coffin describes how the findings fit with what scientists know about XMRV. Copyright © 2009 National Public Radio®. For personal, noncommercial use only. See Terms of Use. For other uses, prior permission required. IRA FLATOW, host: You're listening to SCIENCE FRIDAY from NPR News. I am Ira Flatow. Up next, the latest on a mysterious illness called chronic fatigue syndrome. Researchers have been studying people who have been diagnosed with it, trying to figure out what might be causing their symptoms, which range from joint pain, debilitating fatigue and inflammation. A team of researches reports that - the team report that they hit - they've hit on something. Out of 101 people diagnosed with chronic fatigue, 67 percent of them had a specific virus in their blood: a virus called XMRV. And just four percent, or so, of healthy volunteers had the virus in their blood. Scientists have known about the virus for a while. It's been implicated in other diseases. Joining me now to talk more about this work, published in the journal Science, is John Coffin, professor of molecular biology and microbiology at Tufts University in Boston. Welcome to SCIENCE FRIDAY, Dr. Coffin. Dr. JOHN COFFIN (Professor of molecular biology and microbiology, Tufts University, Boston): Good afternoon, Ira. Thank you. FLATOW: So, this is a pretty good indication, a pretty good connection? Dr. COFFIN: For a first report, it's very good, in fact. There's still a lot of work to be done, to firmly establish a causal relationship between the virus and the disease. But it's a very, very interesting first step. FLATOW: Well, this would also vindicate a lot of people who have chronic fatigue syndrome who have, you know, been abused by people who think it's all in your head, you've got something else, it's just a syndrome, there's no real cause to it. Things like that. Dr. COFFIN: I would imagine that's the case, yes. FLATOW: Mm-hmm. And so how did you go about - what was your motivation for looking for this viral connection? Dr. COFFIN: I have to make one thing very clear right here. The work we're discussing was not mine. It was done by other groups. I'm a very interested observer and chronicler of their work. And I had worked on this virus many years ago when we thought it was just a mouse virus. The people that did work on it, my understanding is that their motivation was based on a correlation that had been previously reported - this virus in a certain specific mutation in individuals with prostate cancer in a gene called RNA cell(ph). FLATOW: Mm-hmm. How many more people would need to be studied, do you think? Do you need a much larger study to make a better, more symmetrical... Dr. COFFIN: Well, we certainly need much a larger study - that's absolutely called for. We don't know very much about the association, except for the 101 people you just mentioned. And my understanding is there's over a million people diagnosed with chronic fatigue syndrome, or suspected to have chronic fatigue syndrome in the United States alone. It's... FLATOW: Is it... Dr. COFFIN: ...possible there are multiple diseases that have very similar symptoms. And there's all kinds of things that are possible here that we just haven't sorted out yet. FLATOW: Yeah. Is it possible that the virus is a red herring, in a way? And I mean, by that, that people with chronic fatigue may have some other problem that leaves them susceptible to getting this virus. Dr. COFFIN: Oh, that's entirely possible. And this all needs to be sorted out. And I think it will be sorted out very quickly, probably within the next few months. FLATOW: Where do you find the virus in the body? Dr. COFFIN: The virus, so far, has been found in white blood cells, principally. And it's been possible, by the groups who are doing this, to actually isolate and grow virus from those cells, and to grow it in new cells of the same type from healthy donors. FLATOW: Mm-hmm. Dr. COFFIN: So we don't know - it's been isolated from those cells because those are, in a sense, the easiest cells to look at. You can just take some blood and then get them out of it. We don't know what other cells it is and isn't in, in infected individuals at this point. FLATOW: And the virus has been implicated in other diseases? Dr. COFFIN: There's an implication with - of prostate cancer. There was a paper that appeared about a month, or so, ago, providing a somewhat less striking -about a 25 percent incidence of the virus in cases of prostate cancer. FLATOW: Mm-hmm. Do we know where it comes from? Dr. COFFIN: Well, it almost has to come from mice. It's very, very closely related to what's called an endogenous virus of mice. An endogenous virus is a retrovirus that's inherited in the DNA, in the germ line of its host. And we have been studying - this is a virus we have been studying for over 25 years now, in mice - never thinking that it might, in fact, also be in humans. FLATOW: Hmm. 1-800-989-8255 is our number. Also you can tweet us, @scifri. In the 101 patients, or in the total study of all the patients, were they split equally among different ages or did you find that the virus was in older or younger people or certain people of certain age? Dr. COFFIN: I don't believe - again, it wasn't my study. FLATOW: Mm-hmm. Dr. COFFIN: My understanding is there wasn't any obvious connection of that sort. But I don't know that for sure, I have to admit. FLATOW: Is there any way to get rid of this virus once it's in your bloodstream? Dr. COFFIN: Probably not. A retrovirus like - HIV is also a retrovirus and there's no way to get rid of HIV that we know of, despite the fact that we have tried very, very hard over many years to do so. HIV infection can be suppressed and people can be relieved of the symptoms of the disease for very long periods of time, but nobody, as far as we know, has ever really been proven to be cured of the infection. And I suspect the same thing will prove to be true with this virus as well. FLATOW: Mm-hmm. You write in an article, or I'm going to quote from an article from Science Express, that another notable feature of XMRV is that the frequency of infection in non-disease controls is remarkably high, about four percent... Dr. COFFIN: Right. FLATOW: ...in both normal individuals from the same geographic region as infected patients. It would mean that, perhaps, it says, 10 million people in the U.S. and hundreds of millions worldwide are infected with this virus. Dr. COFFIN: That's the implication. That's, again, a very initial study on just a few people and one needs to give a much larger sample and some real demographics and so on to establish those numbers. But that's certainly what that would imply as we look at the numbers if we take those numbers at face value right now... FLATOW: Mm-hmm. Dr. COFFIN: ...that would be about 10 times the number of people in the United States who are infected with HIV, for example. FLATOW: Mm-hmm. Mm-hmm. Are you being inundated with people or do you feel that people are going to want to be tested now? Dr. COFFIN: I've gotten a few emails. There are no - I should make it very clear that there are no clinically approved diagnostic tests based on this at present, and it will be some time before such tests are available. Any tests that are being done now are being done purely with research tools, most of which were originally developed to study the mouse virus, as I was talking about. FLATOW: Mm-hmm. And we don't know how the virus is spread? Dr. COFFIN: We have no idea how the virus is spread right now. FLATOW: And - but we know that it's in mice. Dr. COFFIN: It is in mice. All mice carry some virus like it in their DNA. And some, at least in laboratory mice, some express it as infectious virus. How -and it almost certainly, as I said, came from mice originally. How it got from mice to humans, again, we have no idea yet. FLATOW: Let me get a phone call or two in here. Let's go to Bobby(ph) in San Francisco. Hi, Bobby. BOBBY (Caller): Hi. Really enjoy your program, Ira. FLATOW: Thank you. BOBBY: I've had chronic fatigue syndrome now since my 40s. I'm 72. And I wonder if the individual you're talking to has heard of the work of Dr. Nancy Klimas, K-L-I-M-A-S, or the recent studies which found over 350 genetic expression anomalies in chronic fatigue patient syndromes? Oh, pardon me if I'm confused a little bit there. FLATOW: Okay. Dr. COFFIN: I haven't heard of that work specifically, no. It certainly wouldn't surprise me to hear that there's a lot of differences in gene expression in patients - such patients. FLATOW: The fact that this is - this is a retrovirus, what does that say to you? Dr. COFFIN: The fact that it's a retrovirus means it's a virus that replicates in a very specific way by converting its genome RNA to DNA, causing that DNA to be integrated in - with the cellular genome to become essentially normal cellular gene. And then that gene directs the production of more virus. There are many different types of retroviruses. HIV is one. There's a virus called human T-cell leukemia virus which is responsible for some cases of leukemia and lymphoma in human. And then there's a very large number of other viruses in this general group. FLATOW: Can you explain the nomenclature XMRV to describe this? Dr. COFFIN: X comes from xenotropic. It's a slightly confusing designation. What it means is that the virus is found as an endogenous virus, meaning it's in the germline of its host, in this case, mice. But it can't - but if you take the virus out of the germline and make - take the DNA out and make virus out of it, that virus will not infect mice. And therefore - but it will infect humans and many other species of animals, but not mice. And the reason for that is that mice - after the virus got into the germline of mice, after - which is probably around a million years ago or so - the mice became resistant to it by accumulating a mutation which made them no longer able to be infected by that virus. FLATOW: So - and so, it worked its way into the human population? Dr. COFFIN: And somehow, it's worked its way into the human population. FLATOW: Mm-hmm. So do we think it's much more prevalent than we might think otherwise? Dr. COFFIN: Well, the estimated prevalence right now is that four percent number that we're discussing earlier. Whether there's more than that, what -how real that number is and so on... FLATOW: Yeah. Dr. COFFIN: ...we just have to find out a real - good studies have to be done to establish that. FLATOW: All right, Dr. Coffin. I'll thank you for taking time to be with us. Dr. COFFIN: You're very welcome. FLATOW: Good luck to you. John Coffin, a professor of molecular biology and microbiology at Tufts University in Boston, and author of "A New Virus for Old Diseases?" That's in the Science Express paper. (Soundbite of music) Copyright ©2009 National Public Radio®. All rights reserved. No quotes from the materials contained herein may be used in any media without attribution to National Public Radio. This transcript is provided for personal, noncommercial use only, pursuant to our Terms of Use. Any other use requires NPR's prior permission. Visit our permissions page for further information. NPR transcripts are created on a rush deadline by a contractor for NPR, and accuracy and availability may vary. This text may not be in its final form and may be updated or revised in the future. Please be aware that the authoritative record of NPR's programming is the audio. COMUNICADO DE LAS AUTORIDADES SANITARIAS NORUEGAS Norway - National Health Institute on XMRV October 2009 image Retrovirus Found in ME patients Published 23.10.2009 , updated: 23.10.2009, 15:01 U.S. scientists have discovered the retrovirus XMRV in patients with chronic fatigue syndrome (ME). It is too early to draw broad conclusions, but the findings can in the long term have implications for prevention and treatment of disease. On 8 October the renowned scientific journal Science announced that a group of American researchers has found genetic material (DNA) from a virus in white blood cells in a group of patients with chronic fatigue syndrome or myalgic encephalomyelitis (ME). 68 of 101 (67%) patients who were included in the survey had the virus while only 8 of 218 (3.7%) healthy controls had it. The researchers also found that the white blood cells from patients could transmit the virus to a cell culture of other white blood cells. "We think this is a very interesting discovery, "says director Geir Stene-Larsen. "If this virus is contributing to some people developing ME, it may have great significance for the possibilities to prevent and treat the illness. But it is important to emphasise that this is still at a research stage. The U.S. study was small, only 101 patients, and there still remains much research to be done before we can draw some conclusions about the effect the virus has on the development of ME. But this is a field of research which we will follow with great interest the future, "he says. Stene-Larsen emphasises that ME is a serious disorder. It is estimated that 17 million people worldwide are affected and many of the sick have a greatly reduced quality of life. It is a disease we know little about. Therefore, any new knowledge is valuable. Del NYT Virus Is Found in Many With Chronic Fatigue Syndrome SIGN IN TO RECOMMEND TWITTER SIGN IN TO E-MAIL PRINT REPRINTS SHARECLOSE O LINKEDINDIGGFACEBOOKMIXXMYSPACEYAHOO! BUZZPERMALINK By DENISE GRADY Published: October 8, 2009 Many people with chronic fatigue syndrome are infected with a little known virus that may cause or at least contribute to their illness, researchers are reporting. Fred Friedberg, assistant professor at Stony Brook University Hospital in New York, answers your questions about chronic fatigue syndrome. Go to Consults » Related Health Guide: Chronic Fatigue The syndrome, which causes prolonged and severe fatigue, body aches and other symptoms, has long been a mystery ailment, and patients have sometimes been suspected of malingering or having psychiatric problems rather than genuine physical ones. Worldwide, 17 million people have the syndrome, including at least one million Americans. An article published online Thursday in the journal Science reports that 68 of 101 patients with the syndrome, or 67 percent, were infected with an infectious virus, xenotropic murine leukemia virus-related virus, or XMRV. By contrast, only 3.7 percent of 218 healthy people were infected. Continuing work after the paper was published has found the virus in nearly 98 percent of about 300 patients with the syndrome, said Dr. Judy A. Mikovits, the lead author of the paper. XMRV is a retrovirus, a member of the same family of viruses as the AIDS virus. These viruses carry their genetic information in RNA rather than DNA, and they insert themselves into their hosts’ genetic material and stay for life. Dr. Mikovits and other scientists cautioned that they had not yet proved that the virus causes the syndrome. In theory, people with the syndrome may have some other, underlying health problem that makes them prone to being infected by the virus, which could be just a bystander. More studies are needed to explain the connection. But Dr. Mikovits said she thought the virus would turn out to be the cause, not just of chronic fatigue, but of other illnesses as well. Previous studies have found it in cells taken from prostate cancers. “I think this establishes what had always been considered a psychiatric disease as an infectious disease,” said Dr. Mikovits, who is research director at the Whittemore Peterson Institute in Reno, a nonprofit center created by the parents of a woman who has a severe case of the syndrome. Her co-authors include scientists from the National Cancer Institute and the Cleveland Clinic. Dr. Mikovits said she and her colleagues were drawing up plans to test antiretroviral drugs — some of the same ones used to treat HIV infection — to see whether they could help patients with chronic fatigue. If the drugs work, that will help prove that the virus is causing the illness. She said patients and doctors should wait for the studies to be finished before trying the drugs. Dr. William Schaffner, an infectious disease expert at Vanderbilt University, said the discovery was exciting and made sense. “My first reaction is, ‘At last,’ ” Dr. Schaffner said. “In interacting with patients with chronic fatigue syndrome, you get the distinct impression that there’s got to be something there.” He said the illness is intensely frustrating to doctors because it is not understood, there is no effective treatment and many patients are sick for a long time. He added, “This is going to create an avalanche of subsequent studies.” Hallado un vínculo entre el retrovirus XMRV y el SFC El descubrimiento de una relación entre el retrovirus XMRV y el Síndrome de Fatiga Crónica da esperanzas para un diagnóstico definitivo y para posibles tratamientos 6 votos 20 comentarios Jordi Calm | Padrino del foro Fibrodiario | 15/10/2009 | Actualizada a las 10:40h | Participación Investigadores del Instituto Instituto Whittermore Peterson (WPI) en Reno, Estados Unidos, institución dedicada a la investigación de enfermedades neuroinmunes junto con el Instituto Nacional de Cáncer (NCI), parte de los Institutos Nacionales de Salud y la Clínica Cleveland, han descubierto que el 95% de los pacientes con síndrome de fatiga crónica presentan una infección en la sangre por el retrovirus XMRV. MÁS INFORMACIÓN Enlace: Fibromiàlgia i Síndrome de Fatiga Crònica a la família PALABRAS CLAVE Salud, Estados Unidos, Cáncer Los científicos, dirigidos por Vincent Lombardi, descubrieron el retrovirus humano XMRV, inicialmente en 68 de 101 muestras de sangre tomadas de pacientes con síndrome de fatiga crónica, aunque también identificaron el retrovirus en ocho muestras de 218 pacientes sanos. Estudios posteriores han aumentado a un 95% los positivos por este retrovirus en las muestras de personas afectadas de SFC y FM. El retrovirus XMRV que tiene similitud genética con el virus de la leucemia en ratones, se ha encontrado también en células de cáncer de próstata en hombres afectados de una anormalidad genética en el sistema inmune. Este hallazgo demuestra que existe una muy posible asociación entre XMRV y SFC, pero no prueba todavía que XMRV sea el causante del Síndrome de fatiga crónica. Estos datos convincentes pueden permitir el desarrollo de una hipótesis sobre la causa de esta enfermedad compleja y mal entendida, ya que los retrovirus son una causa conocida de enfermedades neurodegenerativas y de cáncer en el hombre además de activar un gran número de virus latentes. Podemos estar delante de las primeras opciones para el tratamiento vital de millones de pacientes. Según Dan Peterson, MD, director médico de WPI, "Para los pacientes con síndrome de fatiga crónica podrían cambiar bastantes las cosas en cuestiones de salud como en el deterioro de su calidad de vida. Estoy muy entusiasmado con la posibilidad de proporcionar a los pacientes que den positivo para XMRV, un diagnóstico definitivo, y esperamos que muy pronto, opciones a tratamientos eficaces". Ahora les toca a los médicos y a la administración comenzar la importante labor de contrastar este descubrimiento y profundizar en las investigaciones. Y ello implica que las unidades especializadas que se están abriendo para atender estas patologías se doten del personal y recursos suficientes para afrontar los cambios que de este descubrimiento y los que le sigan, se pudieran derivar y que finalmente se empiece a invertir realmente en investigación. La revista Science, la más respetada revista científica, que nunca antes había publicado nada sobre el Síndrome de Fatiga Cronica (SFC), ha dado la campanada. Esperemos que finalmente los enfermos tengan el reconocimiento que se merecen y nunca más un médico pueda volver a decir que esto no es una enfermedad.