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Herpesviruses

D- virology. Herpesviruses. Herpes simplex I & II (cold sores, genital herpes) Varicella zoster (chicken pox, shingles) Cytomegalovirus (microcephaly, infectious mono) Epstein-Barr virus (mononucleosis, Burkitt’s lymphoma) Human herpesvirus 6 & 7 (Roseola)

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Herpesviruses

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  1. D- virology Herpesviruses Herpes simplex I & II (cold sores, genital herpes) Varicella zoster (chicken pox, shingles) Cytomegalovirus (microcephaly, infectious mono) Epstein-Barr virus (mononucleosis, Burkitt’s lymphoma) Human herpesvirus 6 & 7 (Roseola) Human herpesvirus 8 (Kaposi’s sarcoma)

  2. Cold Sores

  3. Zoster

  4. Roseola

  5. Human Herpesviruses Virus Subfamily Disease Site of Latency Herpes Simplex Virus Iα Orofacial lesions Sensory Nerve Ganglia Herpes Simplex Virus IIα Genital lesions Sensory Nerve Ganglia Varicella Zoster Virusα Chicken Pox Sensory Nerve Ganglia Recurs as Shingles Cytomegalovirusβ Microcephaly/Mono Lymphocytes Human Herpesvirus 6β Roseola Infantum CD4 T cells Human Herpesvirus 7β Roseola Infantum CD4T cells Epstein-Barr Virus γ Infectious Mono B lymphocytes, salivary Human Herpesvirus 8γ Kaposi’s Sarcoma Kaposi’s Sarcoma Tissue

  6. Herpes Simplex Virus Prototype of group

  7. Virion stabiliy • Enveloped virus • Sensitive to dessication • Easily inactivated by detergents and lipid solvents

  8. Virion structure • Enveloped, spherical virion • Icsoahedral capsid 120 - 200 nm • >12 virally encoded glycoproteins • Tegument proteins

  9. Genome structure • Linear double-stranded DNA • 120 - 230 kb • Genetic complexity -- isomers

  10. Genome structure • Linear double-stranded DNA • 120 - 230 kb • Genetic complexity • # of genes

  11. Replication • Penetration by fusion with plasma membrane • Nuclear site of replication • 80 or so viral proteins are expressed in regulated fashion: • IE - immediate early • E - Early • L - Late • Capsids assemble in nucleus and bud through nuclear membrame

  12. Life-long Latency

  13. Three manifestations of HSV latency • Key Feature: there is a wide spectrum of clinical presentations • Some individuals (5 - 10%) have frequent clinical reactivation • Most individuals reactivation is clinically asymptomatic • In ALL cases, virus is shed

  14. Transmission of HSV-1 and HSV-2 • Skin to skin contact • The virus does not penetrate intact skin • Mild abrasion or chapping of skin can allow infection

  15. Tissue tropism of HSV-1 and HSV-2 • HSV-1: • Causes 95% of orofacial herpes (remainder caused by HSV-2) • Causes 10 - 30% of primary genital herpes (but seldom recurs there) • HSV-2: • Causes primary and recurrent genital herpes infections • May cause primary oral herpes but, like HSV-1 in genital area, it seldom recurs there

  16. Eczema/Herpes

  17. Herpes Simplex Virus type 2 • Infects the genital tract • Is sexually transmitted • Complicates childbirth

  18. Diagnosis of Herpes Simplex Virus Infections: • Viral Culture • Tzanck prep • Culture with monoclonal antibody staining • Serology • Polymerase chain reaction (PCR)

  19. Spectrum of HSV recurrence • Asymptomatic shedding • Shedding with clinically apparent lesions

  20. A study of HSV-2 recurrence in women

  21. Asymptomatic Shedding of HSV • Occurs in both HSV-1 and HSV-2 • The only form of shedding in 1/2 to 2/3 of infected patients • Involves low amounts of virus • Accounts for most transmissions to infected contacts and neonates • Is not completely suppressed by acyclovir

  22. 2/3

  23. 2/3 of the acquisitions of genital herpes come from clinically asymptomatic partners

  24. Alpha Herpesviruses Site of Latency Herpes Simplex Virus type 1 Sensory neurons Herpes Simplex Virus type 2 Sensory neurons Varicella Zoster Virus Sensory neurons Beta Herpesviruses Cytomegalovirus Lymphocytes Human Herpesvirus 6 CD4 T cells Human Herpesvirus 7 CD4 T cells Gamma Herpesviruses Epstein-Barr Virus B lymphocytes Human Herpesvirus 8 Sarcoma tissue

  25. Two Unique Features of VZV: • Airborne spread or skin to skin contact • More severe infection if primary infection occurs as an adult

  26. Complications of Varicella • Reye’s Syndrome • Bacterial Superinfection of lesions (more common in younger patients) • Varicella pneumonia • Neonatal varicella -- disseminated, 30% mortality

  27. Varicella Pneumonia Age Fatalities per 100,000 <1 6.23 1 - 14 0.75 15 - 19 2.70 30 - 49 25.20

  28. Varicella patients at risk • ADULTS • PREGNANCY (3rd trimester) • IMMUNOCOMPROMISED • The mortality rate for varicella pneumonia in leukemic children receiving chemotherapy is 1,000 times higher than in healthy children. • Note: Children with isolated agammaglobulinemia are not at risk!

  29. Neonatal Varicella

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