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M. Tvorko The Herpesviruses • All members show latency and cause recurrent infection – more severe with advancing age, cancer chemotherapy, or other conditions that compromise the immune defenses • Large enveloped icosahedral dsDNA • Replicates within nucleus Herpesviridae • large Family; 8 infect humans – – – – – – – – HSV-1 HSV-2 VZV CMV EBV HHV-6 HHV-7 HHV-8 Epidemiology of Herpes Simplex Viruses • Transmission – direct exposure to secretions containing the virus – active lesions most significant source – genital herpes can be transmitted in the absence of lesions • HSV multiplies in sensory neurons, moves to ganglia – HSV-1 enters 5th cranial nerve – HSV-2 enters lumbosacral spinal nerve trunk ganglia Epidemiology of Herpes Simplex Viruses • Recurrent infection triggered by various stimuli – fever, UV radiation, stress, mechanical injury • Newly formed viruses migrate to body surface – produce a local skin or membrane lesion Type 1 Herpes Simplex (HSV – 1) • Herpes labialis – fever blisters, cold sores – most common recurrent HSV-1 infection – vesicles occur on mucocutaneous junction of lips or adjacent skin – itching and tingling prior to vesicle formation – lesion crusts over in 2-3 days and heals • Herpetic gingivostomatitis – infection of oropharynx in young children – fever, sore throat, swollen lymph nodes • Herpetic keratitis – ocular herpes Type 2 Herpes Simplex (HSV – 2) • Genital herpes – herpes genitalia – starts with malaise, anorexia, fever, and bilateral swelling and tenderness in the groin – clusters of sensitive vesicles on the genitalia, perineum, and buttocks – urethritis, painful urination • Recurrent bouts usually less severe – triggered by menstruation, stress, and concurrent bacterial infection Herpes of the Newborn • HSV-1 and HSV-2 • Potentially fatal in the neonate and fetus • Infant contaminated by mother before or during birth • hand transmission by mother to infant • Infection of mouth, skin, eyes, CNS • Preventative screening of pregnant women – delivery by C-section if outbreak at the time of birth Diagnosis, Treatment, and Control • Vesicles and exudate are typical diagnostic symptoms • scrapings from base of lesions showing giant cells – culture and specific tests for diagnosing severe or disseminated HSV • direct fluorescent antibody tests • Treatment – acyclovir, famciclovir, valacyclovir; topical medications Varicella-Zoster Virus (VZV) • virus enters neurons & remains latent • later reactivation of the virus results in shingles with vesicles localized to distinctive areas – dermatomes • treatment – acyclovir, famciclovir, interferon • live attenuated vaccine Epstein-Barr Virus (EBV) • HSV-4 • infects lymphoid tissue & salivary glands • transmission – direct oral contact & contamination with saliva • by mid-life 90-95% of all people are infected • causes mononucleosis – sore throat, high fever, cervical lymphadenopathy • Complications include: – – – – heart defects facial paralysis rupture of the spleen jaundice (hepatitis) Epstein-Barr Virus (EBV) • 30-50 day incubation • most cases asymptomatic • Burkitt’s lymphoma – associated with chronic coinfections with malaria • nasopharyngeal carcinoma in Chinese & African men Human Herpes Virus 6 • HHV-6 • T-lymphotropic virus • transmitted by close contact • very common • causes roseola – an acute febrile disease in babies 2-12 months • can cause encephalitis, cancer Human Herpes Virus 6 • begins with fever, followed by a faint maculopapular rash • usually self-limited • adults may get mono-like symptoms, lymphadenopathy, hepatitis • over 70% of MS patients show signs of infection Diseases of the Skin Caused by Herpesviruses HEPATITIS B VIRUS: HEPATITIS B VIRUS: HBV SPREAD MAINLY BY PARENTERAL ROUTE • DIRECT PERCUTANEOUS INOCULATION OF INFECTED SERUM OR PLASMA • INDIRECTLY THROUGH CUTS OR ABRASIONS • ABSORPTION THROUGH MUCOSAL SURFACES • ABSORPTION OF OTHER INFECTIOUS SECRETIONS (SALIVA OR SEMEN DURING SEX) HBV SPREAD MAINLY BY PARENTERAL ROUTE • POSSIBLE TRANSFER VIA INANIMATE ENVIRONMENTAL SURFACES • VERTICAL TRANSMISSION SOON AFTER CHILDBIRTH (TRANSPLACENTAL TRANSFER RARE) • CLOSE, INTIMATE CONTACT WITH AN INFECTED PERSON WHO IS AT GREATEST RISK FOR HBV INFECTION? • LAB PERSONNEL WORKING WITH BLOOD PRODUCTS • SEXUALLY ACTIVE HOMOSEXUALS • PERSONS WITH MULTIPLE AND FREQUENT SEX CONTACTS • MEDICAL/DENTAL PERSONNEL HBV - Diagnosis Acute Infection HBV DNA HBeAg Anti-HBe Anti-HBs AntiHBc HBsAg 0 Anti-HBc IgM 2 Months 4 6 Years HBV - Vaccine Vaccine Engerix-B Recombivax HB (Optional 2-dose) Age Group Dose Volume # Doses (ug) (ml) 0-19 yr 20 yr Adults on hemodialysis 10 20 0.5 1.0 3 (mo 0,1,6) 3 (mo 0,1,6) 40 2.0 4 (mo 0,1,2,6) 0-19 yr 20 yr 11-15 yr Adults on hemodialysis 5 10 10 0.5 1.0 1.0 3 (mo 0,1,6) 3 (mo 0,1,6) 2 (mo 0, 4-6) 40 1.0* 3 (mo 0,1,6) Adenoviruses 1949. Enders et al.: first cell cultures for cultivation of polioviruses 1953. Rowe et al.: removed tonsills for tissue culture „blind” passages cytopathic effect (roundish cells) normal (healthy) cell culture AD (Adenoid Degeneration) APC (Adenoidal-PharygealConjuctival) ARD (Acute Respiratory Disease) RI (Respiratory Illness) ADENOVIRUS (1956) adenovirus virions • nonenveloped, ds DNA • 30 types associated with human disease • infect lymphoid tissue, respiratory & intestinal epithelia & conjunctiva • oncogenic in animals, not in humans • spread by respiratory & ocular secretions • causes colds, pharyngitis, conjunctivitis, keratoconjunctivitis, acute hemorrhagic cystitis • inactivated polyvalent vaccine • Inclusion bodies VIRION: icosahedral, 80-90 nm 252 capsomers: 12 fibers at the vertices, 240 hexons, 12 structural proteins (polypeptides) NUCLEIC ACID: ds DNA REPLICATION in cytoplasm, virion assembly in the nucleus CLASSIFICATION OF ADENOVIIRUSES Genera: Aviadenovirus (birds), Ataadenovirus (reptiles, ruminants, birds, brush-tail possum) Siadenovirus (frog, birds) Ichtadenovirus (new, fish) MASTADENOVIRUS (vertebrates animals: more than 100 serotypes, 52 human serotypes) MASTADENOVIRUS GENUS Groups (previosly: Subgenera, grouping based on lenght of fiber, G/C content of DNA, agglutination of red blood cells (HA), oncogenicity) A highly oncogenic (types 12, 18, 31) B weekly oncogenic (types 3,7, 11, 14,16, 21, 34, 35, 51) C cell transformation in tissue culture (types 1, 2, 5, 6) D cell transformation in tissue culture (types 8-10, 13, 15, 17, 19, 20, 22-30, 32, 33, 36-39, 42-50) E none (type 4) F ? (types 40, 41) G (new group) ? (type 52) DISEASES CAUSED BY ADENOVIRUSES DIFFERENT SEROTYPES - SAME DISEASE SAME SEROTYPE - DIFFERENT DISEASES RESPIRATORY TRACT INFECTIONS: pharyngitis: types 1,2,3,5,7, acute respiratory disease of recruits: types 4, 7,14, 21 pharyngoconjunctival fever: types 3,7 pneumonia: 1,2,3,7 pertussis-like syndrome: type 5 EYE INFECTIONS : pharyngoconjunctival fever (conjunctivitis), epidemic keratoconjunctivitis: types 8,19,37 (swimming pool, nosocomial: eye droplets, tonometer) in all age group follicular conjunctivitis: 3,4,11 ENTERIC INFECTIONS: second in causative agents causing gastroenteritis in infants (AV types 40, 41, the first one is rotavirus) and AV type 53 in adults diagnozis: EM, ELISA or latex agglutination Urinary tract infections: acute haemorrhagic cystitis: types 11, 21 (children, young adults) INFECTIONS IN IMMUNO-COMPROMISED PATIENTS: encephalitis, pneumonia, gastroenteritis, generalized disease (type 5 and new serotypes: 34, 35) (PREVENTION: „live” adenovirus serotypes 4 and 7 in enterosolvent capsule) RECOMBINANT ADENOVIRUSES (GENE THERAPY) DNA Introduction of foreign genes (malignant diseases, diseases based on gene defects) immune therapy (cytokin genes), moleculare therapy (tumor suppressor genes), virus therapy PARVOVIRUSES Parvus: very small VIRION: icosahedral, 20-25 nm NUCLEIC ACID: (-) DNA REPLICATION: in the nucleus, with the help of cellular enzymes CLASSIFICATION: Family: PARVOVIRIDAE Subfamily: PARVOVIRINAE Genera: ERYTRHOVIRUS (B19) Bocavirus (human bocavirus) Parvovirus (RA-1) Dependovirus (requires helper virus : AAV, Adenovirus Associated Virus) Densovirus (animal pathogens) adenovirus AAV ERYTHEMA IINFECTIIOSUM „FIIFTH DIISEASE” (morbiillllii,, chiickenpox,, rubelllla,, scarllet fever ) • Human parvovirus B19 (respiratory droplets, seasonality: autumn, winter, high % of seropositivity) • special affinity to red blood cells (haematological changes) • severe situation in chronic anaemia • in pregnancy: spontaneous abortion, malformations Papillomavirus • papilloma – benign, squamous epithelial growth, wart or verruca • caused by 100 different strains of HPV • common seed warts – Fingers • plantar warts – soles of feet • genital warts – prevalent STD • transmissible through direct contact or contaminated fomites • Incubation – 2 weeks – more than a year Genital Warts • most common STD in US • over 6 M new cases each year • 30 M carriers of one of the 5 types of HPV associated with genital warts • strong association with cervical & penile cancer – type 16 & 18 • Treatment – podophyllin chemical treatment, cauterization, freezing, laser surgery, immunotherapy