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DNA -VIRUSES

DNA -VIRUSES. 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.

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DNA -VIRUSES

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  1. DNA -VIRUSES M. Tvorko

  2. 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

  3. Herpesviridae large Family; 8 infect humans HSV-1 HSV-2 VZV CMV EBV HHV-6 HHV-7 HHV-8

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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)

  12. Epstein-Barr Virus (EBV) 30-50 day incubation most cases asymptomatic Burkitt’s lymphoma associated with chronic co-infections with malaria nasopharyngeal carcinoma in Chinese & African men

  13. 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

  14. 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

  15. Diseases of the Skin Caused by Herpesviruses

  16. HEPATITIS B VIRUS:

  17. HEPATITIS B VIRUS:

  18. 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)

  19. 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

  20. 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

  21. Acute Infection HBV DNA HBeAg Anti-HBe Anti-HBs Anti-HBc HBsAg Anti-HBc IgM 0 2 4 6 Months Years HBV - Diagnosis

  22. Vaccine Age Group Dose Volume # Doses (ug) (ml) Engerix-B 0-19 yr 10 0.5 3 (mo 0,1,6)  20 yr 20 1.0 3 (mo 0,1,6) Adults on hemodialysis 40 2.0 4 (mo 0,1,2,6) Recombivax HB 0-19 yr 5 0.5 3 (mo 0,1,6)  20 yr 10 1.0 3 (mo 0,1,6) (Optional 2-dose) 11-15 yr 10 1.0 2 (mo 0, 4-6) Adults on hemodialysis 40 1.0* 3 (mo 0,1,6) HBV - Vaccine

  23. 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-Pharygeal-Conjuctival) ARD (Acute Respiratory Disease) RI (Respiratory Illness) ADENOVIRUS (1956) adenovirus virions

  24. 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

  25. 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

  26. 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)

  27. 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)

  28. DISEASES CAUSED BY ADENOVIRUSES DIFFERENT SEROTYPES - SAME DISEASE SAME SEROTYPE - DIFFERENT DISEASES

  29. 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

  30. ENTERIC INFECTIONS: second in causative agents causing gastroenteritis in infants (AV types 40, 41, the first one is rotavirus) and AV type 53 inadults 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)

  31. 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

  32. Parvus: very small PARVOVIRUSES 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

  33. 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

  34. 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

  35. 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

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