Introduction to Herpes Viruses

1. Introduction to Herpes Viruses Hugh B. Fackrell Filename: Herpes1.ppt Fackrel@uwindsor.ca

3. Herpes Viruses Group characteristics Herpes simplex 1 Herpes simplex 2

5. VP26 Assembly in HSV-1 Capsid

6. Herpes Virus Outline • Structure • Classification • Multiplication • Clinical manifestations • Epidemiology • Diagnosis • Control Baron’s Web Site

7. Herpes have a Unique Structure • dsDNA core • Iscadeltahedral protein capsid • amorphous tegument • lipid envelope with glycoproteins

8. Human Herpesvirus Subfamilies • herpesvirinae • herpesvirinae • herpesvirinae Infect both vertebrate and non vertebrate >100 types characterized 6 types infect humans

9. Bovine Herpes • Mammillitus

10. Herpesvirinae • Human herpesvirus 1 -HHV1 Herpes simplex type 1-HSV1 • Human Herpesvirus 2 -HHV2 Herpes simplex type 2 -HSV2 Short replicative cycle Rapid cytopathology Broad host range

11. Animations of HSV • Receptor Binding • RNA Transcription in productive infection • Latent Infections • DNA Replication • Encapsidation and Release Click here to view Dr. Ed. Wagner, superb series of animations on HSV on the internet

12. Herpes simplex virus

13. Herpes simplex virus Isolated from a patient with shingles

14. Herpesvirinae • Human Herpesvirus 5 -HHV5 Cytomegalovirus- CMV Long replicative cycle Restricted host range Slow cytopathology

15. Cytomegalovirus

16. Herpesvirinae • Human Herpesvirus 4 HHV4 • Epstein-Barr EBV or EB • Human Herpesvirus 6 -HHV6 Very restricted host range

18. Varicellavirus • genus in herpesvirus family • human herpesvirus 3 (HHV3) • varicella-zoster virus

19. Multiplication Genes replicated in specific order • Immediate early genes • regulatory proteins • Early genes • enzymes for replicating viral DNA • Late genes • structural proteins Occurs in host cell nucleus

20. Latent Infections • ALL herpes viruses can establish latent infections. The viral genome may become incorporated into the host DNA or remain extrachromosomal • Latent viruses can be reactivated by stress, menstruation or uv light • Reactivation may be asymptomatic or lead to mild or severe disease.

21. Diagnosis • Isolation of virus by tissue culture • herpevirinae cause cytopathic effects • intranuclear fluorescence of scrapings using fluorescent antibodies • PCR being developed CMV retinitis is diagnosed clinically

22. Prevention of Herpesvirus • Vaccines • VZV vaccine being licensed • HSV1, HSV2, & CMV vaccines being developed • Passive immunization • pooled immunoglobulin • hyperimmune globulin

23. Anti-herpesvirus drugs • Idoxuridine- herpetic keratitis • Trifuridine-herpetic keratitis • Vidarabine - wide range of applications • Acylovir-wide range of applications • Ganciclovir -CMV

24. Herpes Simplex Viruses

25. Epidemiology of Herpes Simplex • HSV1 is transmitted by kissing or other contact with saliva • HSV2 is spread by sexual contact • HSV2 is spread nosocomially

26. Mucocutaneous infections caused by Herpes simplex • Gingivostomatis • Herpes simplex labialis (cold sores) • Genital herpes • Keratitis • Whitlows- health care workers • Herpes gladiatorum- wrestlers

27. Herpes simplex type 1 • Herpes labialis. • cold sores or fever blisters. text: page 569. • 2-12 day incubation period. • gingivostomatitis -- vesicles rupture. • latent virus in ganglia -- Herpetic keratoconjunctivitis -- ulcers can be identified by fluorescein staining.

28. Herpes simplex • Stomatitis

29. Herpes simplex

30. Herpes simplex • Stomatitis

31. Transmission: HSV1 • Transmitted by direct contact such as kissing or fondling; very common with young children. • Good personal hygiene does curtail the transmission.

32. Treatment HSV1 • The first drugs were used to treat conjunctivitis and keratitis • Iododeoxyuridine • trifluridine • adenine arabinoside • acyclovir

33. Treatment HSV1 • Iododeoxyuridine: direct application to the cornea • Trifluridine, Keratitis: direct application • Adenine arabinoside: direct application to the cornea. Intravenously injected, it reduces mortality from herpes encephalitis. • Acyclovir: is now the drug of choice, is the least toxic. Can be used topically, orally and intravenously.

34. Genital Herpes HSV2 • primary infection: vulva, vagina, cervix.glans penis, prepuce or penile shaft. • fever, malaise, anorexia, bilateral inguinal adenopathy. • sexually transmitted - highest rate among young adults. • Patients on immunosuppressive drugs

35. Neonatal Herpes Simplex • infants acquire the virus passing through the birth canal. • disseminated herpes - newborns; premature infants susceptible

36. Herpes Simplex Encephalitis

37. Treatment HSV2 • Acyclovir does not cure the initial infection, but because it prevents the attachment of released virus from an infected cell, it ameliorates the disease. With aggressive treatment eventually the viruses disappear. It is not an effective cure for the latent stage.

38. Herpes simplex infection of egg membranes

39. Herpes Intranuclear inclusions

40. Herpes simplex Syncytia

41. Ctyopathic effect Early Late>