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Classification Of Virus[Summary]
 

Classification Of Virus[Summary]

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    Classification Of Virus[Summary] Classification Of Virus[Summary] Presentation Transcript

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