DNA Viruses

1. DNA Viruses H – erpesviridae (HSV 1 & 2, VZV, EBV, CMV, HHV 6, 7 & 8) H – epadnaviridae (Hepatitis B virus) A – denoviridae (Adenoviruses 1-47) P – arvoviridae (B19) P – apovaviridae (papillomaviruses, Bk, JC) P – oxviridae (smallpox, Molluscum contagiosum) y

2. DNA VIRUSES • All DNA viruses except the parvoviruses are double-stranded. • All except the poxviruses replicate in the nucleus. • All except the poxviruses are icosahedral.

3. PARVOVIRUS Fifth disease (erythema infectiosum) • often infects adolescents • mild fever and recurring slapped cheek appearance with lacy rash on arms and body (indistinguishable from rubella) • Chronic anemia in immunocompromised patients, aplastic crises in sickle cell patients and hydrops fetalis

4. PAPOVAVIRUSES Papillomaviruses (warts) • transmitted by direct contact • HPV 1 & 4 – plantar warts, benign • HPV 6 & 11 – most common cause of anogenital warts (condylomata acuminata – STI) and laryngeal warts, benign but regrow after removal • HPV 16 & 18 – cervical intraepithelial carcinoma

5. PAPOVAVIRUSES Polyomaviruses • cause disease only in immunocompromised patients BK – cause kidney disease, often associated with kidney transplantation JC –associated with progressive multifocal leukoencephalopathy

6. POXVIRUSES • Brick-shaped complex appearance • Only DNA virus that makes all nucleic acids in the cytoplasm and carries its own polymerase • Produces cytoplasmic inclusion bodies

7. POXVIRUSES • Variola – cause of smallpox eradicated in 1977 • Vaccinia – immunogen used in the vaccine • Molluscum contagiosum – cause benign, pincushionlike, pink tumors • With nipplelike indentations

8. ADENOVIRUSES Pharyngo and keratoconjunctivitis • conjunctiva inflamed with watery exudate but not purulent Acute respiratory diseases • most serious - interstitial pneumonitis in immunocompromised Gastroenteritis • Adenovirus 40 and 41

9. HEPADNAVIRUS • “serum” hepatitis • Parenteral or sexual transmission • Insidious onset common • Associated with primary hepatocarcinoma and cirrhosis

10. Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms anti-HBe HBeAg Total anti-HBc Titre anti-HBs IgM anti-HBc HBsAg Window period 0 4 8 12 16 24 28 32 52 100 20 36 Weeks after Exposure

11. Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titre IgM anti-HBc Years 0 4 8 16 20 24 28 36 12 32 52 Weeks after Exposure

12. HERPESVIRUSES • Only viruses assembled in the nucleus of the infected cell • Only viruses whose envelope is from host cell nuclear membrane • HSV and VZV both become latent in neurons

13. Herpes simplex viruses • May cause acute or latent infections • In latent infections, the immediate early proteins (alpha) are expressed but beta viral proteins (thymidine kinase and DNA polymerase) are not made. • Acyclovir not effective against latent HSV infections because it target the DNA polymerase

14. HSV-1 • Infection seen usually above the waist • Infections often asymptomatic • Can cause the following: • Gingivostomatitis – initial manifestion; recur as cold sores or fever blisters • Herpetic whitlow – finger or nail area • Keratoconjunctivitis – may lead to blindness • Encephalitis – common cause of sporadic form

15. HSV-2 • Infection usually seen below the waist • Sexually transmitted • Maybe asymptomatic or may cause painful primary outbreaks seen as vesicular lesions • Can cause serious neonatal disease: • Localized to skin, eyes or mouth • Generalized involving many organs • Localized to CNS without other manifestations

16. Varicella zoster • Primary infection is known as chickenpox; secondary infection – herpes zoster or shingles • Mild febrile disease and asynchronous rash (papular lesion, vesiculate, pustules, formation of crust) • Contagious for 6 days after all lesions have dried • Treatment: VZIG and oral acyclovir

17. Cytomegalovirus • Extremely common • Transmission: across placenta, during birth or through mother’s milk, direct contact with others, sexual contact or blood • Produces large purple intranuclear inclusion bodies surrounded a halo (“owl’s eye”) • Most infections are asymptomatic but maybe mononucleosis-like in adults

18. Cytomegalovirus • Clinical disease: Immunocompromised patients - severe • Retinitis • Interstitial pneumonitis Neonates • Cytomegalic inclusion disease – hepatosplenomegaly with thrombocytopenic purpura, pneumonitis and CNS calcifications and microcephaly

19. Epstein-Barr virus • Infects by binding to the CD21 molecules on human B lymphocytes • Unique: formation of heterophile antibodies which react with animal RBC antigens • Infectious mononucleosis • Common in 15-25 year olds in the US • Fatigue, pharyngitis/tonsilitis, lymphadenopathy, hepatomegaly and splenomegaly

20. RNA Viruses B – unyaviridae (Rift Valley, Sin Nombre, Hantaan) A – renaviridae (Lassa, Lymphocytic choriomeningitis virus) T – ogaviridae (Rubella, Chikungunya, Equine encephalitis viruses) O – rthomyxoviridae (Influenza virus types A, B, C) F – laviviridae (Yellow fever, dengue, Japanese encephalitis, West Nile, Hepatitis C) F – iloviridae (Ebola and Marburg)

21. RNA Viruses P – aramyxoviridae (Parainflu 1-4, measles, mumps, RSV) P – icornaviridae (Polio, Coxsackie, Echo, Hepatitis A virus) R – eoviridae (Rotaviruses) R – etroviridae (HTLV 1 and 2, HIV 1 and 2) R – habdoviridae (Rabies, Vesicular stomatitis) C – aliciviridae (Noroviruses, Hepatitis E) C – oronaviridae (SARS)

22. POSITIVE SS RNA VIRUSES • Carry the genetic code for the RdRp but not the polymerase protein in the mature virion • Naked (+) ss RNA is infectious. • Replicate in the cytoplasm except retroviruses • None of the viruses is segmented • All are enveloped except caliciviruses and picornaviruses

23. PICORNAVIRUSES • Naked, icosahedral: hard to inactivate with disinfectants or organic solvents • Members: • Enteroviruses (polio, coxsackie A and B, echoviruses, enterovirus 68-71) • Heptovirus – hepatitis A • Rhinoviruses – acid labile

24. Polioviruses • Types 1, 2 and 3 • Infects oral and gastrointestinal tract; cause paralytic disease when anterior horn of the spinal cord is infected • 90 – 95% of infection asymptomatic • Vaccines: Sabin (attenuated) and Salk (killed)

25. Coxsackie A and B, Echoviruses, Enterovirus 68-71 • Upper respiratory infections • Colds, herpangina, stomatitis • Rashes and vesicles – hand-foot-mouth disease • CNS infections – meningitis (common) • Gastrointestinal disorders • Hemorrhagic conjunctivitis • Myopericarditis – primarily caused by Cox B

26. Hepatitis A • “infectious” hepatitis • Onset generally abrupt, disease mild • Fecal-oral, often foodborne • No chronic infections

27. Rhinoviruses • Cause of common colds • Restricted to upper respiratory tract • Acid labile, grow better at 35oC

28. CALICIVIRUSES • Norwalk gastroenteritis • Noninflammatory diarrhea • Older children and adults • Potluck meals, contaminated shellfish, water-borne

29. CALICIVIRUSES • Hepatitis E • “enteric” hepatitis • Fecal-oral, often foodborne • Onset abrupt, disease mild • No chronic infections • 20% mortality in pregnant women

30. FLAVIVIRUSES • Hepatitis C • “post-transfusion” hepatitis • Parenteral or sexual transmission • Acute disease usually subclinical • High rate of chronicity • Associated with primary hepatocellular carcinoma and cirrhosis

31. FLAVIVIRUSES • Yellow fever • Spread by mosquitoes • Cause febrile disease, can include hepatitis and may progress to hemorrhagic fever • Available vaccine is attenuated • St. Louis encephalitis • Arbovoviral disease • Most severe in the elderly

32. FLAVIVIRUSES • Dengue • Breakbone disease • Spread by Aedes mosquitoes • Serious forms: DHF and DSS • Japanese encephalitis virus • Spread by Culex mosquitoes • 50% with neurologic disorders

33. TOGAVIRUSES • Alphaviruses • Western, eastern and Venezuelan equine encephalitis viruses • Mosquito-spread • Wild bird – normal hosts horses and man – incidental, accidental, dead-end hosts

34. TOGAVIRUSES • Rubella virus • Cause German measles • Discrete red maculopapular rash, lymphadenopathy and mild fever • Can cross placenta and cause serious birth defects (cataracts, retinopathy, sensorineural deafness)

35. CORONAVIRUSES • Large, enveloped and helical • Envelope with hemagglutinin • Virus resembles a crown (”corona”) • Second most common cause of common cold • Sars-Cov – emerging cause of pneumonia

36. RETROVIRUSES – HIV • Diploid genome • Carry reverse transcriptase, integrase and protease • Regular genes: gag, env and pol • Accessory genes: tat, rev, vif, vpu,nef • AIDS – characterized by opportunistic infections

37. NEGATIVE SS RNA VIRUSES • Negative-sense RNa is the homolog of mRNA • All carry a virion-associated RdRp • Genome of uncoated virion not infectious • All viruses are helical and enveloped • Segmented: Ortho, Bunya and Arena

38. PARAMYXOVIRUSES • Generally have single serotypes except for paramyxoviruses (4 serotypes) • All are transmitted via respiratory secretion, directly or by fomites

39. Measles • Also known as rubeola • Has hemagglutinin and fusion proteins • Fever, cough, coryza, conjunctivitis, Koplik’s spots on oral mucosa, erythematous maculopapular rash (starts on face and moves down)

40. Measles • Complications: • Otitis media • Bronchopneumonia with giant cells • Diarrhea • Vaccine is attenuated strain • Treatment of malnourished children with Vit. A increases survival

41. Mumps • Has combined HN and fusion protein • Disease caused includes salivary gland enlargement where most cases show meningeal signs and orchitis (rarely causes sterility) • Attenuated vaccine available

42. Parainfluenza virus • Has combined HN and fusion protein • Causes croup (laryngotracheobronchitis) in infants, URIs, pneumonia and bronchiolitis • No vaccine

43. Respiratory syncytial virus • Contains only a Fusion protein • infants and young children - major cause of bronchiolitis and pneumonia • Older children, adolescents and adults - cause colds with bronchitis

44. RHABDOVIRUSES • Bullet-shaped • Preventable but fatal when virus has reached CNS • Vaccine and immunoglobulins available • Pathognomonic: presence of eosinophilic intracytoplasmic inclusion bodies (Negri bodies)

45. FILOVIRUSES • “thread”, filamentous viruses • Cause hemorrhagic fever; starts with influenza-like symptoms, then vomiting, and diarrhea; ends with bleeding, shock and death • Members: Ebola and Marburg

46. ORTHOMYXOVIRUSES • Influenza A, B, and C • Contains H and N proteins in envelope • H – 16 subtypes; N – 9 subtypes • Influenza A – associated with epidemics and pandemics, only one with animal hosts • Antigenic drift – errors in RdRp, need for yearly vaccination • Antigenic shift – genetic reassortment; double infection of two influenza strains from different hosts

47. BUNYAVIRUSES • Segmented, enveloped, helical • With ambisense genome • California encephalitis virus • Spread by Aedes mosquitoes • Causes subclinical infections or occasionally nonfatal encephalitis in school-aged children • Hantavirus (Sin nombre hantavirus) • Influenza-like presentation leading to acute respiratory syndrome • Transmitted in deer mice feces and urine

48. ARENAVIRUSES • Enveloped with two helical segments (one negative and the other ambisense) • Lymphocytic choriomeningitis (LCM) • Influenza-like disease with meningitis • Unlike most viral meningitis, LCM may be fatal • Lassa fever • Febrile disease which is complicated by hemorrhage

49. DOUBLE STRANDED RNA VIRUSES • Reoviridae Family • Naked, double-shelled capsid • Rotaviruses -major cause of infantile diarrhea (noninflammatory, prolonged diarrhea in infants younger than 2 years of age) • Colorado tick fever virus – cause viral encephalitis • Reovirus – exposure common in humans; may cause febrile disease

50. THANK YOU.