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Ch. 19 Human Herpes Viruses

Ch. 19 Human Herpes Viruses. HERPESVIRUSES. Herpes Simples Virus type 1 (HSV-1) Herpes Simples Virus type 2 (HSV-2) Varicella-Zoster Virus (VZV) Cytomegalovirus (CMV) Epstein-Barr Virus (EBV) Human Herpesvirus 8 (HHV-8) or Kaposi‘s Sarcoma-Associated herpesvirus) (KSHV).

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Ch. 19 Human Herpes Viruses

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  1. Ch. 19Human Herpes Viruses

  2. HERPESVIRUSES • Herpes Simples Virus type 1 (HSV-1) • Herpes Simples Virus type 2 (HSV-2) • Varicella-Zoster Virus (VZV) • Cytomegalovirus (CMV) • Epstein-Barr Virus (EBV) • Human Herpesvirus 8 (HHV-8) or Kaposi‘s Sarcoma-Associated herpesvirus) (KSHV)

  3. HERPESVIRUSES • All are icosahedral enveloped viruses • ds linear DNA genome • Large viruses (120-200 nm) • Replicate in the nucleus (budding) • Cause latent infections • HSV-1&2 and VZV cause vesicular rash

  4. HERPESVIRUSES • According to type of infected tissues and latency, it can be subdivided to: * α-herpesviruses (HSV-1 & 2, VZV) ,infect epithelial cells (latency in neurons) *β-herpesviruses (CMV, HHV-6), infect variety of tissues *γ- herpesviruses (EBV, HHV-8), infect lymphoid cells

  5. 1- Herpes Simplex Viruses (HSV) • HSV-1 causes acute gingivostomatitis, cold sores, keratoconjunctivitis & encephalitis • HSV-2 causes genital herpes, neonatal herpes & aseptic meningitis • Both types can be distinguished by RE & monoclonal Abs • Human is the natural host

  6. Replication • The virus attaches to its receptor • After entry, uncoated occur and the genome DNA enters the nucleus • DNA changes from linear to circular • Early mRNA transcribed by host RNA polymerase • Early nonstructural proteins translated • Viral DNA polymerase replicates the genome DNA

  7. Replication Cont. • Late protein synthesis bgins • Transported to the nucleus • Assembly occurs • Envelope obtained from the nuclear membrane • Leave cells by lysis or via tubules (cell-cell ) • Latent infection (only few genes transcribed)

  8. Transmission & Epidemiology • HSV-1: saliva • HSV-2: sexual contact • Asymptomatic infections plays important role in transmission • Primary infections mostly by HSV-1 in childhood

  9. Pathogenesis & Immunity • Initiates infection in skin • Migrates and latent in the sensory ganglion cells • Reactivation occurs by many reasons • Multinucleated giant cells (vesicle) • Immunity is incomplete • Cell-mediated immunity is important

  10. Clinical Findings • Gingivostomatitis:primary infection is more severe but may be asymptimatic • Herpes labialis: crops of vesicles

  11. Clinical Findings cont. • Keratoconjunctivitis:corneal ulcers & lesions • Encephalitis: has a high mortality rate • Herpetic whitlow: pustule lesion on the skin

  12. Keratoconjunctivitis

  13. Clinical Findings cont. • Genital herpes: painful vesicular lesions • Neonatal herpes: may be mild or severe, mothers with primary infection are more infective than with recurrent infections

  14. DISEASE

  15. Lab. Diagnosis • Tissue culture (CPE in 1-3 days) • DFA or ELISA • Rapid diagnosis by Tzanck smear(giemsa) • PCR assay (specially in encephalitis) • Serologic assay:TORCH

  16. Treatment • Acyclovir • For eye infections: trifluridine (viroptic) are used topicallly. • Valacyclovir (valtrex) & famciclovir (famvir) are used for genital herpes • Penciclovir: recurrent orolabial HSV-1

  17. 2- Varicella-Zoster Virus (VZV) • Primary disease: varicella, recurrent form is chingles • Only one serotype • Humans are the natural hosts • Replication cycle is like HSV Transmission electron micrograph of varicella- zoster virions from vesicle fluid of patient with chickenpox

  18. Transmission & Epidemiology • Respiratory droplets • Direct contact to the lesions • > 90% in USA children are seropositive • Highly contagious disease (very important in hospitals in case of immunocompromised patients)

  19. Pathogenesis & Immunity • 1st infect the mucosa of URT, then spread via blood to the skin • Causing vesicular rash (M.Ncl. Giant cell) • Latency occurs in dorsal root ganglia • Reactivation causes vesicular skin lesions & nerve pain of zoster • Immunity is lifelong (varicella),(Zoster??)

  20. Clinical Findings • Varicella:IP (14-21 days), prodromal symptoms are fever & malaise. A papulovesicular rash appears, develop to vesicles, pustules and then crusts • More sever in adults • Reye‘s syndrome (encephalopathy & liver degeneration)

  21. Clinical Findings cont. • Zoster (Shingles ): a painful vesicles along the course of a sensory nerve of the head or trunk

  22. Lab. Diagnosis • Clinically • Tzanck smear • Cell culture

  23. Treatment • No antiviral is needed in case of immunocompetent children • Acyclovir for adults • Also for immunocompromised • Foscarnet for acyclovir-VZV resistant strains

  24. Prevention • Vaccination by live attenuated VZV (Varivax) • One dose for children 1-12y. • Teenagers need 2 doses • Prophylaxis using acyclovir or VZIG

  25. 3- Cytomegalovirus (CMV) • The most common cause of congenital abnormalities in USA • It causes also pneumonia in immunocomp. • Only one serotype • Giant cells are formed and human is the natural host

  26. Transmission & Epidemiology • Across the placenta • During birth • Breast milk feeding • Via saliva (children) • or sexually • also via blood transfusion or organ transpl. • > 80% adults are seropositive

  27. Pathogenesis & Immunity • Fetus infection cause cytomegalic inclusion disease in many organs • Congenital abnormalities occure (1st trimester) • Asymptomatic infections (adults & children) • Latency occurs in leukocytes & kidneys • It causes inhibiting for T cells • Host defenses include both humoral & cell-mediated immunity

  28. Clinical Findings • ~ 20% of infants show microcephaly, deafness,jaundice & purpura • Hepatosplenomegaly • In adults, heterophil-negative mononucleosis • Systemic infections?? Owl‘s-eye shape H&E stain of lung section showing nuclear inclusions

  29. Lab. Diagnosis • Cell cultures (shell vials) • Immunofluorescent Abs • PCR • 4-fold increase in Abs H&E stain of CMV-infected cells in lung of AIDS patient Specimen of human embryonic lung reveals the presence of cytomegalovirus using immunofluorescent technique

  30. Treatment • Ganciclovir (Cytovene) • Valganciclovir (orally) • Foscarnet (Foscavir) • Largely resistant to acyclovir • Fomivirsen (Vitravene), anti-sense DNA approved for treatment of CMV retinitis

  31. 4- Epstein- Barr Virus • Infectious mononucleosis • Burkitt's lymphoma • Nasal pharyngeal carcinoma • B-cell lymphomas • Hairy leukoplakia

  32. Transmission & Epidemiology • Exchange of saliva • Blood transmission is very rare • One of the most common infection • > 90% of adults in USA are seropositive

  33. Pathogenesis & Immunity • Primary infection occurs in oropharynx • Then, infect the B-lymphocytes • EBV remains latent within B-lymphocytes • 1st immune response is IgM (VCA) • Followed by lifelong IgG (VCA) • Nonspecific heterophil antibodies are found • These Abs are also seen in Hepatitis B and serum sickness

  34. Clinical Findings • The primary infection is often asymptomatic • Symptoms include fever, sore throat, lymphadenopathy & splenomegaly • 2 other diseases: 1- severe form of I.M. In X-linked lymphoproliferative syndrome (mortality rate is high „75%“ by age 10) 2- hairy leukoplakia in AIDS patients

  35. Oral hairy leukoplakia of tongue in AIDS Tongue and palate of patient with infectious mononucleosis Conjunctival hemorrhage due to infectious mononucleosis Burkitt's Lymphoma

  36. Laboratory diagnosis • Hematologic approach:absolute lymphocytosis (atypical lymphs) • Immunologic approach: a) Heterophil antibody test (Monospot test) b) EBV-specific Abs tests: - IgM VCA - IgG VCA

  37. Treatment & Prevention • For mild infections, no need for aniviral drugs • Acyclovir has little activity against EBV • no vaccine

  38. 5- Human Herpesvirus 8 (HHV-8) • HHV-8 was reported in 1994 • formerly known as Kaposi's sarcoma associated herpes virus • The most common cancer in AIDS patients • It resembles lymphotropic herpesviruses more than neutropic one • In general population, the prevalence of HHV-8 in USA is ~ 3% but in east Africa is ~ 50%

  39. It causes malignant transformation (inactivation of RB by nuclear antigen protein) • Transmission occurs sexually & also by organs trasplantation • Lab Dx of KS is made by biopsy • Virus is not grown in culture • Treated by surgical excision, radiation, α-interferon or vinblastine • But there is no specific antiviral drug or vaccine

  40. 6- Human herpes virus 6 • This virus is found worldwide • Is found in the saliva of the majority of adults (>90%) • it replicates in B and T lymphocytes with inclusions in both cytoplasm and nucleus • infection is life-long, and the virus can reactivate in immune-suppression. • It causes roseola infantum ( a common disease of young children ) • In adults, primary infection is associated with a mononucleosis

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