1. Medical Microbiology Chapter 54 Human Herpesviruses

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

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

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

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

6. Human Herpesviruses Infection progression: Infection progression: Enters tissue through breaks in mucous membranes or skin Enters tissue through breaks in mucous membranes or skin Infects cells at the base of the break Infects cells at the base of the break Replicates and spreads to surrounding tissue Replicates and spreads to surrounding tissue Sometimes syncytia are formed to facilitate spread Sometimes syncytia are formed to facilitate spread Neurons are infected and the virus travels to ganglia (trigeminal-oral; sacral;genital) Neurons are infected and the virus travels to ganglia (trigeminal-oral; sacral;genital) The virus goes into a latent state 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 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 This leads to viral replication and movement back down the nerve to infect the same area Subsequent infections are usually more mild (memory) Subsequent infections are usually more mild (memory)

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

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

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

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

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

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

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

15. Human Herpesviruses The viruses go into latency in the dorsal root ganglia (or cranial nerve ganglia) 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 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) This causes shingles or “herpes zoster” (zoster means belt or girdle) The virus only infects the specific dermatome innervated by the nerve The virus only infects the specific dermatome innervated by the nerve Figure 54-11 Figure 54-11 Box 54-6 Box 54-6

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

17. Human Herpesviruses Treatment – live, attenuated vaccine Treatment – live, attenuated vaccine

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

19. Human Herpesviruses Immuno-competent individuals have mono Immuno-competent individuals have mono Lack of effective immune control of EBV leads to the proliferative diseases 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. 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) Huge numbers of lymphocytes in the blood account for the name (mononucleosis) Virus persists in a few B-cells for life! Virus persists in a few B-cells for life!

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

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