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Basic virus structure Capsid protein Nucleocapsid Naked capsid virus = + Nucleocapsid Lipid membrane, glycoproteins Envelo...
Properties of enveloped viruses <ul><li>Envelope is sensitive to </li></ul><ul><ul><li>Drying </li></ul></ul><ul><ul><li>H...
Properties of naked capsid viruses <ul><li>Capsid is resistant to </li></ul><ul><ul><li>Drying </li></ul></ul><ul><ul><li>...
Classification of Human Viruses www.freelivedoctor.com
Variations on the replication theme www.freelivedoctor.com
Summary: structure, classification & replication <ul><li>Structure </li></ul><ul><ul><li>Nucleic acid in a protein shell, ...
Summary: laboratory virology <ul><li>4 main clinical diagnostic techniques </li></ul><ul><ul><li>Culture, serology, antige...
Cycle of infection Secondary sites Spread Entry Shedding Shedding Local Lymphatic Neuronal Blood (viremia) Primary site ww...
Time course of infection; host response infection without spread: infection with spread: host response: www.freelivedoctor...
Patterns of disease www.freelivedoctor.com
Summary: Pathogenesis & Genetics <ul><li>Cycle of infection </li></ul><ul><li>Effects on cells </li></ul><ul><ul><li>Abort...
For each virus, know: <ul><li>Structure (cheat sheet) </li></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>transmission/en...
Human papillomavirus <ul><li>Structure </li></ul><ul><ul><li>Small (8 kb) circular dsDNA genome, naked capsid </li></ul></...
Parvovirus <ul><li>Structure </li></ul><ul><ul><li>Small (5 kb) linear ssDNA genome, naked capsid </li></ul></ul><ul><li>P...
Polyomavirus <ul><li>Structure </li></ul><ul><ul><li>Small (5 kb) circular dsDNA genome, naked capsid </li></ul></ul><ul><...
Adenovirus <ul><li>Structure </li></ul><ul><ul><li>Medium sized (36 kb) dsDNA genome, naked capsid </li></ul></ul><ul><li>...
Influenza <ul><li>Structure </li></ul><ul><ul><li>Negative sense segmented ssRNA genome, helical nucleocapsid, enveloped <...
Paramyxoviruses <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA genome, helical nucleocapsid, envelope with a...
<ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA, helical nucleocapsid, envelope </li></ul></ul><ul><li>Pathog...
Rotavirus <ul><li>Structure </li></ul><ul><ul><li>Naked double shell capsid </li></ul></ul><ul><ul><li>11 segment double s...
Summary www.freelivedoctor.com
Paramyxoviruses <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA genome, helical nucleocapsid, envelope with a...
Rabies <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA, helical nucleocapsid, envelope </li></ul></ul><ul><li...
Time course of Rabies infections www.freelivedoctor.com
Rotavirus <ul><li>Structure </li></ul><ul><ul><li>Double stranded, 11 segment RNA genome, two protein coats </li></ul></ul...
Enteroviruses <ul><li>Structure </li></ul><ul><ul><li>Positive sense ssRNA genome, protein coat </li></ul></ul><ul><li>Pat...
www.freelivedoctor.com
Arboviruses <ul><li>Structure </li></ul><ul><ul><li>Positive sense ssRNA genome, icosahedral nucleocapsid, enveloped </li>...
Arboviruses: Vectors, Hosts, and Diseases www.freelivedoctor.com
Rubella virus <ul><li>Structure </li></ul><ul><ul><li>Positive sense ssRNA genome, helical nucleocapsid, enveloped </li></...
RNA Hepatitis Viruses <ul><li>Structure </li></ul><ul><li>Various different families for HAV, HCV, HEV, HGV all positive s...
HGV Flavi ///////////hepe www.freelivedoctor.com
Hepatitis B Virus <ul><li>Structure </li></ul><ul><ul><li>Small (3.2 kb) circular partially dsDNA genome, envel. capsid </...
Hepatitis B virus www.freelivedoctor.com
Immunological events of acute vs. chronic HBV infection From Murray et. al., Medical Microbiology 5 th  edition, 2005, Cha...
Clinical interpretation of the Hepatitis B antigen panel www.freelivedoctor.com
Hepatitis D Virus <ul><li>Structure </li></ul><ul><ul><li>Very Small (1.7 kb) circular ssRNA genome, envel. capsid </li></...
HIV <ul><li>Structure </li></ul><ul><ul><li>9.0 kb diploid ssRNA genome, envel. capsid </li></ul></ul><ul><li>Pathogenesis...
HIV-1 Replication Cycle CCR5 CD4 CXCR4 Reverse Transcriptase Integrase Protease Beth D. Jamieson, Ph.D. www.freelivedoctor...
Natural Course of HIV-1 Infection www.freelivedoctor.com
Herpesviruses Herpes simplex I & II  (cold sores, genital herpes) Varicella zoster  (chicken pox, shingles) Cytomegaloviru...
Virus   Subfamily   Disease   Site of Latency Herpes Simplex Virus I    Orofacial lesions  Sensory Nerve Ganglia Herpe...
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www.freelivedoctor.com
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FDA approved antiviral drugs www.freelivedoctor.com
Non-equilibrium human virus <ul><ul><ul><ul><li>1. Virus has a stable relationship with an animal host. </li></ul></ul></u...
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Classification Of Virus[Summary]

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  1. 1. Basic virus structure Capsid protein Nucleocapsid Naked capsid virus = + Nucleocapsid Lipid membrane, glycoproteins Enveloped virus + www.freelivedoctor.com DNA RNA or
  2. 2. Properties of enveloped viruses <ul><li>Envelope is sensitive to </li></ul><ul><ul><li>Drying </li></ul></ul><ul><ul><li>Heat </li></ul></ul><ul><ul><li>Detergents </li></ul></ul><ul><ul><li>Acid </li></ul></ul><ul><li>Consequences </li></ul><ul><ul><li>Must stay wet during transmission </li></ul></ul><ul><ul><li>Transmission in large droplets and secretions </li></ul></ul><ul><ul><li>Cannot survive in the gastrointestinal tract </li></ul></ul><ul><ul><li>Do not need to kill cells in order to spread </li></ul></ul><ul><ul><li>May require both a humoral and a cellular immune response </li></ul></ul>Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5 th edition, Elsevier Mosby, Philadelphia, PA Box 6-5 www.freelivedoctor.com
  3. 3. Properties of naked capsid viruses <ul><li>Capsid is resistant to </li></ul><ul><ul><li>Drying </li></ul></ul><ul><ul><li>Heat </li></ul></ul><ul><ul><li>Detergents </li></ul></ul><ul><ul><li>Acids </li></ul></ul><ul><ul><li>Proteases </li></ul></ul><ul><li>Consequences </li></ul><ul><ul><li>Can survive in the gastrointestinal tract </li></ul></ul><ul><ul><li>Retain infectivity on drying </li></ul></ul><ul><ul><li>Survive well on environmental surfaces </li></ul></ul><ul><ul><li>Spread easily via fomites </li></ul></ul><ul><ul><li>Must kill host cells for release of mature virus particles </li></ul></ul><ul><ul><li>Humoral antibody response may be sufficient to neutralize infection </li></ul></ul>Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5 th edition, Elsevier Mosby, Philadelphia, PA , Box 6-4 www.freelivedoctor.com
  4. 4. Classification of Human Viruses www.freelivedoctor.com
  5. 5. Variations on the replication theme www.freelivedoctor.com
  6. 6. Summary: structure, classification & replication <ul><li>Structure </li></ul><ul><ul><li>Nucleic acid in a protein shell, +/- lipid envelope </li></ul></ul><ul><ul><li>Structure impacts on biological properties </li></ul></ul><ul><li>Classification </li></ul><ul><ul><li>Many virus families, organized by structure and biology </li></ul></ul><ul><li>Replication </li></ul><ul><ul><li>Generic scheme </li></ul></ul><ul><ul><li>Varying strategies depending on nucleic acid </li></ul></ul>www.freelivedoctor.com
  7. 7. Summary: laboratory virology <ul><li>4 main clinical diagnostic techniques </li></ul><ul><ul><li>Culture, serology, antigen detection, nucleic acid detection </li></ul></ul><ul><li>Virus culture </li></ul><ul><ul><li>Cultured cell types </li></ul></ul><ul><ul><li>Cytopathic effect </li></ul></ul><ul><ul><li>Not all viruses can be cultured </li></ul></ul><ul><li>Virus quantitation </li></ul><ul><ul><li>Biological </li></ul></ul><ul><ul><li>Physical </li></ul></ul><ul><li>Basic serological techniques </li></ul>www.freelivedoctor.com
  8. 8. Cycle of infection Secondary sites Spread Entry Shedding Shedding Local Lymphatic Neuronal Blood (viremia) Primary site www.freelivedoctor.com
  9. 9. Time course of infection; host response infection without spread: infection with spread: host response: www.freelivedoctor.com 0 2 4 6 8 10 12 time (days)
  10. 10. Patterns of disease www.freelivedoctor.com
  11. 11. Summary: Pathogenesis & Genetics <ul><li>Cycle of infection </li></ul><ul><li>Effects on cells </li></ul><ul><ul><li>Abortive, lytic, persistent, latent, transforming infections </li></ul></ul><ul><li>Effects on the organism </li></ul><ul><li>Genetics </li></ul><ul><ul><li>Mutation, genotype, phenotype, reversion, recombination </li></ul></ul>www.freelivedoctor.com
  12. 12. For each virus, know: <ul><li>Structure (cheat sheet) </li></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>transmission/entry/shedding </li></ul></ul><ul><ul><li>replication </li></ul></ul><ul><ul><li>spread </li></ul></ul><ul><ul><li>immune response/counter response </li></ul></ul><ul><ul><li>damage/disease mechanism </li></ul></ul><ul><li>Diagnosis </li></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>drugs </li></ul></ul><ul><ul><li>vaccines </li></ul></ul>www.freelivedoctor.com
  13. 13. Human papillomavirus <ul><li>Structure </li></ul><ul><ul><li>Small (8 kb) circular dsDNA genome, naked capsid </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>transmission by direct contact or sexual; skin, mucosa </li></ul></ul><ul><ul><li>replication in nucleus of basal cells of epithelium; very host dependent; coupled to epithelial differentiation </li></ul></ul><ul><ul><li>no spread </li></ul></ul><ul><ul><li>primarily cellular immune response </li></ul></ul><ul><ul><li>transforming infection; warts are tumors; cervical carcinoma </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>cytology (PAP smear; koilocytosis) </li></ul></ul><ul><ul><li>immunohistochemistry </li></ul></ul><ul><ul><li>nucleic acid </li></ul></ul><ul><li>Prevention/treatment </li></ul><ul><ul><li>recombinant subunit (VLP) vaccine </li></ul></ul><ul><ul><li>PAP smear </li></ul></ul><ul><ul><li>surgery </li></ul></ul>www.freelivedoctor.com
  14. 14. Parvovirus <ul><li>Structure </li></ul><ul><ul><li>Small (5 kb) linear ssDNA genome, naked capsid </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>respiratory transmission </li></ul></ul><ul><ul><li>replication in nucleus, very host dependent, needs S phase cells or helper virus </li></ul></ul><ul><ul><li>viremia </li></ul></ul><ul><ul><li>antibody important in immunity </li></ul></ul><ul><ul><li>targets erythroid lineage cells; fifth disease (symptoms immunological); transient aplastic crisis; hydrops fetalis </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>serology, viral nucleic acid </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>none </li></ul></ul>www.freelivedoctor.com
  15. 15. Polyomavirus <ul><li>Structure </li></ul><ul><ul><li>Small (5 kb) circular dsDNA genome, naked capsid </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>respiratory transmission </li></ul></ul><ul><ul><li>replication in nucleus; very host dependent </li></ul></ul><ul><ul><li>viremia </li></ul></ul><ul><ul><li>persistence in kidneys; reactivation with immune compromise </li></ul></ul><ul><ul><li>inapparent infection; hemorrhagic cystitis; PML </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>viral nucleic acid </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>cidofovir ? </li></ul></ul>www.freelivedoctor.com
  16. 16. Adenovirus <ul><li>Structure </li></ul><ul><ul><li>Medium sized (36 kb) dsDNA genome, naked capsid </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>respiratory or fecal oral transmission </li></ul></ul><ul><ul><li>replication in nucleus; moderately host dependent </li></ul></ul><ul><ul><li>local spread; viremia </li></ul></ul><ul><ul><li>cellular and humoral immunity important; virus encodes countermeasures against MHC I expression and apoptosis </li></ul></ul><ul><ul><li>direct cell damage from replication; respiratory illness, conjunctivitis, gastroenteritis, cystitis </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>culture, viral antigen detection </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>live military vaccine </li></ul></ul>www.freelivedoctor.com
  17. 17. Influenza <ul><li>Structure </li></ul><ul><ul><li>Negative sense segmented ssRNA genome, helical nucleocapsid, enveloped </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>respiratory transmission </li></ul></ul><ul><ul><li>replication in nucleus; budding </li></ul></ul><ul><ul><li>no spread (usually) </li></ul></ul><ul><ul><li>innate and antibody response important; antigenic shift and drift </li></ul></ul><ul><ul><li>local symptoms from cell killing; systemic symptoms from immune response; exaggerated disease in young and elderly; viral and bacterial pneumonia complications </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>culture, hemadsorbtion, viral antigen detection </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>amantidine and rimantidine target matrix; zanamivir and oseltamivir target NA </li></ul></ul><ul><ul><li>killed and live vaccines need constant updating </li></ul></ul>www.freelivedoctor.com
  18. 18. Paramyxoviruses <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA genome, helical nucleocapsid, envelope with attachment protein and F protein </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Transmission in respiratory droplets and fusion of virus envelope via F protein with plasma membrane of cells in the respiratory tract </li></ul></ul><ul><ul><li>Replication in cytoplasm, budding </li></ul></ul><ul><ul><li>Viremia except for RSV and PIV </li></ul></ul><ul><ul><li>Innate and antibody response important; many symptoms from immune response: rash in measles and swelling in mumps; PIV bronchitis and croup; RSV bronchiolitis and pneumonia in infants </li></ul></ul><ul><ul><li>Sequelae in CNS for measles and mumps </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Serology or nucleic acid </li></ul></ul><ul><ul><li>Measles: Koplik spots; mumps: swelling of parotid gland </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>MMR live attenuated viral vaccine for measles and mumps, none for RSV or PIV </li></ul></ul>www.freelivedoctor.com
  19. 19. <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA, helical nucleocapsid, envelope </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Transmitted by bite of rabid animal </li></ul></ul><ul><ul><li>Replication in cytoplasm; budding </li></ul></ul><ul><ul><li>Spread by axonal transport to brain; long incubation period </li></ul></ul><ul><ul><li>Fever, nausea, hydrophobia, coma </li></ul></ul><ul><ul><li>Almost always fatal </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Viral antigen or nucleic acid, Negri bodies </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>Inactivated viral vaccine for humans after exposure, live virus vaccine for animals </li></ul></ul>Rabies www.freelivedoctor.com
  20. 20. Rotavirus <ul><li>Structure </li></ul><ul><ul><li>Naked double shell capsid </li></ul></ul><ul><ul><li>11 segment double stranded RNA genome </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Fecal oral transmission </li></ul></ul><ul><ul><li>Replication in cytoplasm </li></ul></ul><ul><ul><li>Fever, vomiting, diarrhea in infants and young children </li></ul></ul><ul><ul><li>Incubation period less than 48 hr, highly infectious </li></ul></ul><ul><ul><li>Infection of intestinal epithelium causes loss of electrolytes and prevents readsorption of water </li></ul></ul><ul><ul><li>Long term immunity; asymptomatic infection in adults </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>viral antigen detection </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>RotaTeq live, oral vaccine </li></ul></ul>www.freelivedoctor.com
  21. 21. Summary www.freelivedoctor.com
  22. 22. Paramyxoviruses <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA genome, helical nucleocapsid, envelope with attachment protein and F protein </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Transmission in respiratory droplets and fusion of virus envelope via F protein with plasma membrane of cells in the respiratory tract </li></ul></ul><ul><ul><li>Replication in cytoplasm, budding </li></ul></ul><ul><ul><li>Viremia except for RSV and PIV </li></ul></ul><ul><ul><li>innate and antibody response important; many symptoms from immune response: rash in measles and swelling in mumps; PIV bronchitis and croup; RSV bronchiolitis and pneumonia in infants </li></ul></ul><ul><ul><li>Sequelae in CNS for measles and mumps </li></ul></ul><ul><li>Diagnosis – serology or nucleic acid </li></ul><ul><ul><li>Measles Koplik spots; mumps swelling of parotid gland </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>MMR live attenuated viral vaccine for measles and mumps, none for RSV or PIV </li></ul></ul>www.freelivedoctor.com
  23. 23. Rabies <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA, helical nucleocapsid, envelope </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Transmitted by bite of rabid animal </li></ul></ul><ul><ul><li>replication in cytoplasm; budding </li></ul></ul><ul><ul><li>Spread by axonal transport to brain; long incubation period </li></ul></ul><ul><ul><li>Fever, nausea, hydrophobia, coma </li></ul></ul><ul><ul><li>Almost always fatal </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Viral antigen or nucleic acid, Negri bodies </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>Inactivated viral vaccine for humans after exposure, live virus vaccine for animals </li></ul></ul>www.freelivedoctor.com
  24. 24. Time course of Rabies infections www.freelivedoctor.com
  25. 25. Rotavirus <ul><li>Structure </li></ul><ul><ul><li>Double stranded, 11 segment RNA genome, two protein coats </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Fecal oral transmission </li></ul></ul><ul><ul><li>replication in cytoplasm </li></ul></ul><ul><ul><li>Epidemic diarrhea in infants and young children- fever, vomiting, diarrhea </li></ul></ul><ul><ul><li>Incubation period less than 48 hr, highly infectious </li></ul></ul><ul><ul><li>Infection of intestinal epithelium causes loss of electrolytes and prevents re-adsorption of water </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>culture, viral antigen detection </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>RotaTeq live, oral vaccine </li></ul></ul>www.freelivedoctor.com
  26. 26. Enteroviruses <ul><li>Structure </li></ul><ul><ul><li>Positive sense ssRNA genome, protein coat </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Fecal oral transmission </li></ul></ul><ul><ul><li>replication in cytoplasm </li></ul></ul><ul><ul><li>Viremia to diverse target tissues. Viruses very cytopathic, killing cells they infect </li></ul></ul><ul><ul><li>Infections often asymptomatic; polio causes paralytic poliomyelitis; rhinoviruses restricted to upper respiratory tract, common cold; caliciviruses diarrhea </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Serology and nucleic acid </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>Only polio vaccines, Salk and Sabin </li></ul></ul>www.freelivedoctor.com
  27. 27. www.freelivedoctor.com
  28. 28. Arboviruses <ul><li>Structure </li></ul><ul><ul><li>Positive sense ssRNA genome, icosahedral nucleocapsid, enveloped </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Transmitted by bite of insect from host species; sylvan and urban cycles </li></ul></ul><ul><ul><li>replication in cytoplasm; budding </li></ul></ul><ul><ul><li>Viremia to target tissue </li></ul></ul><ul><ul><li>Influenza-like initial symptoms; different viruses cause encephalitis, hemorrhagic fever, hepatitis, rash, arthritis </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Serology and nucleic acid </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>No human vaccines, except yellow fever virus live attenuated vaccine, control of insect population </li></ul></ul>www.freelivedoctor.com
  29. 29. Arboviruses: Vectors, Hosts, and Diseases www.freelivedoctor.com
  30. 30. Rubella virus <ul><li>Structure </li></ul><ul><ul><li>Positive sense ssRNA genome, helical nucleocapsid, enveloped </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>respiratory transmission </li></ul></ul><ul><ul><li>replication in cytoplasm; budding </li></ul></ul><ul><ul><li>Viremia </li></ul></ul><ul><ul><li>Mild rash in adults; congenital rubella syndrome (CRS) after infection in first trimester when virus passes the placenta and infects fetus </li></ul></ul><ul><ul><li>CRS- deafness, blindness, mental retardation </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Nucleic acid, viral antigen detection </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>MMR live attenuated virus vaccine </li></ul></ul>www.freelivedoctor.com
  31. 31. RNA Hepatitis Viruses <ul><li>Structure </li></ul><ul><li>Various different families for HAV, HCV, HEV, HGV all positive sense ssRNA </li></ul><ul><li>Pathogenesis </li></ul><ul><li>HAV and HEV fecal oral then viremia; others sexual and blood borne, viremia </li></ul><ul><li>Liver is target organ; most infections are subclinical, acute infections differ in onset and severity. </li></ul><ul><li>HAV and HEV cause hepatitis with no carrier state; others cause hepatitis with chronic infection and possible carcinoma </li></ul><ul><li>Liver damage due to cell mediated immune response </li></ul><ul><li>Diagnosis </li></ul><ul><li>viral antigen detection, nucleic acid </li></ul><ul><li>Treatment/prevention </li></ul><ul><li>HAV killed virus vaccine; HCV alpha-interferon effective for some serotypes </li></ul>www.freelivedoctor.com
  32. 32. HGV Flavi ///////////hepe www.freelivedoctor.com
  33. 33. Hepatitis B Virus <ul><li>Structure </li></ul><ul><ul><li>Small (3.2 kb) circular partially dsDNA genome, envel. capsid </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Sexual, parenteral, and perinatal transmission </li></ul></ul><ul><ul><li>Replication via an RNA intermediate (reverse transcriptase) </li></ul></ul><ul><ul><li>Tropism for liver </li></ul></ul><ul><ul><li>Acute vs. chronic infections occur: highly age dependent </li></ul></ul><ul><ul><li>Chronic infections are a major cause of PHC </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Multiple serological components (viral proteins and anti-bodies) </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>Subunit vaccine (based on HBsAg) </li></ul></ul>www.freelivedoctor.com
  34. 34. Hepatitis B virus www.freelivedoctor.com
  35. 35. Immunological events of acute vs. chronic HBV infection From Murray et. al., Medical Microbiology 5 th edition, 2005, Chapter 66, published by Mosby Philadelphia,, A) Acute B) Chronic www.freelivedoctor.com
  36. 36. Clinical interpretation of the Hepatitis B antigen panel www.freelivedoctor.com
  37. 37. Hepatitis D Virus <ul><li>Structure </li></ul><ul><ul><li>Very Small (1.7 kb) circular ssRNA genome, envel. capsid </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Sexual, parenteral, and perinatal transmission </li></ul></ul><ul><ul><li>Replication by RNA-directed RNA Pol (Host RNA Pol II) </li></ul></ul><ul><ul><li>Requires concurrent HBV infection (needs it for HBsAg) </li></ul></ul><ul><ul><li>HDV greatly exacerbates liver damage caused by HDV </li></ul></ul><ul><ul><li>Chronic infections are a major cause of PHC </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Serologically for HDV delta antigen </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>Subunit vaccine for HBV prevents productive infection </li></ul></ul>www.freelivedoctor.com
  38. 38. HIV <ul><li>Structure </li></ul><ul><ul><li>9.0 kb diploid ssRNA genome, envel. capsid </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Sexual, parenteral, and perinatal transmission </li></ul></ul><ul><ul><li>Replication by cDNA intermediate (reverse transcriptase) </li></ul></ul><ul><ul><li>Replication cycle requires the DNA intermediate to integrate </li></ul></ul><ul><ul><li>HIV establishes a persistent infection that ultimately reduces CD4 helper T cell population </li></ul></ul><ul><ul><li>During course of infection, tropism shift from M-tropic to T-tropic </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Serologically for antibodies against HIV antigens (gp120) </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>Antivirals (HAART) </li></ul></ul>www.freelivedoctor.com
  39. 39. HIV-1 Replication Cycle CCR5 CD4 CXCR4 Reverse Transcriptase Integrase Protease Beth D. Jamieson, Ph.D. www.freelivedoctor.com Reverse Transcription Integration Uncoating Assembly Budding Attachment Maturation
  40. 40. Natural Course of HIV-1 Infection www.freelivedoctor.com
  41. 41. 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) www.freelivedoctor.com
  42. 42. Virus Subfamily Disease Site of Latency Herpes Simplex Virus I  Orofacial lesions Sensory Nerve Ganglia Herpes Simplex Virus II  Genital lesions Sensory Nerve Ganglia Varicella Zoster Virus  Chicken Pox Sensory Nerve Ganglia Recurs as Shingles Cytomegalovirus  Microcephaly/Mono Lymphocytes Human Herpesvirus 6  Roseola Infantum CD4 T cells Human Herpesvirus 7  Roseola Infantum CD4T cells Epstein-Barr Virus  Infectious Mono B lymphocytes, salivary Human Herpesvirus 8  Kaposi’s Sarcoma Kaposi’s Sarcoma Tissue Human Herpesviruses www.freelivedoctor.com
  43. 43. A study of HSV-2 recurrence in women www.freelivedoctor.com
  44. 44. www.freelivedoctor.com
  45. 45. Vaccines – live or killed ? www.freelivedoctor.com
  46. 46. FDA approved antiviral drugs www.freelivedoctor.com
  47. 47. Non-equilibrium human virus <ul><ul><ul><ul><li>1. Virus has a stable relationship with an animal host. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>2. Virus can be strikingly lethal since it hasn’t evolved to coexist with humans. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>3. Virus will be in genetic flux until it reaches equilibrium or human infection chain is broken. </li></ul></ul></ul></ul><ul><li> 4 . HIV, Ebola virus, Hantavirus and Influenza virus are examples </li></ul>www.freelivedoctor.com
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