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Medical Microbiology

Medical Microbiology. Chapter 54 Human Herpesviruses. Human Herpesviruses. Human Herpesviruses – Table 54-1 Structure: Large, enveloped virus – Figure 54-1 Double-stranded DNA genome (linear). Human Herpesviruses. Replication Attachment is very tissue-specific Entry by membrane fusion

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Medical Microbiology

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  1. Medical Microbiology Chapter 54 Human Herpesviruses

  2. Human Herpesviruses • Human Herpesviruses – Table 54-1 • Structure: • Large, enveloped virus – Figure 54-1 • Double-stranded DNA genome (linear)

  3. Human Herpesviruses • Replication • Attachment is very tissue-specific • Entry by membrane fusion • Capsid then delivers DNA to the nucleus • Replication, transcription, translation • New capsids are assembled in the nucleus (around the replicated DNA) • They exit the cell by exocytosis or cell lysis

  4. Human Herpesviruses • Herpes Simplex Virus (HSV) was linked to cold sores in 1919! • Genome codes for ~80 proteins • ~90% of 2-year-olds in developing countries have Ab to HSV-1 • ~22% of adults in the US are infected with HSV-2 (45 million) • There are about 1 million new cases per year

  5. Human Herpesviruses • Herpes Simplex Virus (HSV) infection sites: • Figure 54-3 • HSV-1 usually causes infections above the waist • HSV-2 usually causes infections below the waist • Symptoms are generated from cell lysis and cytotoxic T-cell activity • Antibody effectiveness is limited

  6. Human Herpesviruses • Infection progression: • Enters tissue through breaks in mucous membranes or skin • Infects cells at the base of the break • Replicates and spreads to surrounding tissue • Sometimes syncytia are formed to facilitate spread • Neurons are infected and the virus travels to ganglia (trigeminal-oral; sacral;genital) • The virus goes into a latent state

  7. Human Herpesviruses • Reactivation is triggered by stress, trauma, fever, menstruation, UV exposure, or a suppressed immune system • This leads to viral replication and movement back down the nerve to infect the same area • Subsequent infections are usually more mild (memory)

  8. Human Herpesviruses • Evasion of the immune system: • Blocks effects of interferon • Blocks the cell machinery that is responsible for Ag-presentation on the MHC I protein • Spreads through syncytia to evade Ab

  9. Human Herpesviruses • Transmission (enveloped virus) • Body fluids or close contact • HSV-1 Kissing, sharing glasses, straws, toothbrushes, etc. • HSV-2 – Sexual contact or infection at or before birth • This usually leads to very severe neurological infections and damage in the neonate

  10. Human Herpesviruses • Disease progression – Figure 54-4 • Cold Sores – Figures 54-5 and 54-6 • Genital Herpes – lesions on or around the genitalia • Recurrence is usually preceded by a tingling, burning sensation • Then lesions erupt • This can recur every 2-3 weeks or up to 6 months

  11. Human Herpesviruses • Herpes encephalitis and meningitis • Causes significant morbidity and mortality • HSV neonatal infection – often causes mental retardation and death • No functional Cell-Mediated Immunity

  12. Human Herpesviruses • Treatment (acyclovir and others) can lessen severity and length of disease, but there is no cure • No vaccine is available, but they are in development

  13. Human Herpesviruses • Varicella-Zoster Virus • Shares many characteristics with HSV-1 • Latency, lesions, and Cell-mediated immunity required for clearing

  14. Human Herpesviruses • Disease progression: • Acquired by inhalation (droplet transmission) • Primary infection in mucosa of respiratory tract • Viremia allows spread to liver, spleen, and other tissues • Viral replication continues • Secondary viremia allows spread to the skin with the formation of “chicken pox” • This viremia facilitates spread BEFORE symptoms arise • Figures 54-9 and 54-10

  15. Human Herpesviruses • The viruses go into latency in the dorsal root ganglia (or cranial nerve ganglia) • The virus can be reactivated in older individuals or patients with impaired cell-mediate immunity • This causes shingles or “herpes zoster” (zoster means belt or girdle) • The virus only infects the specific dermatome innervated by the nerve • Figure 54-11 • Box 54-6

  16. Human Herpesviruses • Epidemiology • VZV is extremely communicable (90% rate of household infection) • More than 90% of adults have Ab • 10-20% of infected adults will experience zoster • Disease is much worse in adults and teens because immunopathology is worse • Can lead to pneumonia and death • Box 54-7

  17. Human Herpesviruses • Treatment – live, attenuated vaccine

  18. Human Herpesviruses • Epstein-Barr Virus (EBV) primarily infects B-cells • Causes infectious mononucleosis (“mono”), Hodgkin’s disease, and a type of cancer called Burkitt’s lymphoma • EBV infection: • Replication in B-cells • Latency in B-cells • Immortalize B-cells

  19. Human Herpesviruses • Immuno-competent individuals have mono • Lack of effective immune control of EBV leads to the proliferative diseases • Mono results from a “civil war” between infected B-cells and T-cells. • Huge numbers of lymphocytes in the blood account for the name (mononucleosis) • Virus persists in a few B-cells for life!

  20. Human Herpesviruses • EBV is transmitted in saliva • 90% of EBV-infected persons shed the virus intermittently for life (even though they are asymptomatic)! • 70% of US population infected by age 30 • Boxes 54-8 and 54-9

  21. Human Herpesviruses • Symptoms of mono: • Swollen lymph nodes • Splenomegaly (enlarged spleen) • Exudative pharyngitis (sore throat) • Fever, malaise, FATIGUE • No Treatment

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