Download Hallado un vínculo entre el retrovirus XMRV y el SFC

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
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7. R. Wolff, S. Koller, J. Ruscetti, Virology 43, 472 (1982).
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9. K. A. Smith, F. W. Ruscetti, Adv. Immunol. 31, 137 (1981). [Web of Science]
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10. G. Dunn, K. Sheehan, L. Old, R. Schreiber, Cancer Res. 65, 3447
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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.
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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
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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.