CLS02 - Viruses

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  1. define variolation
    Inhale (inoculate) dried crust from infected pox to produce immunity
  2. Basic viral structure
    • core: RNA or DNA (not both)
    • capsid: protein coat packaging the core
    • nucleocapsid: core + capsid
    • envelope: (not all) membrane w/ host glycolipids/proteins
  3. General steps in viral replication
    • Attachment
    • Entry
    • Uncoating
    • Transcription
    • Translation
    • Replication
    • Assembly
    • Release
  4. Define tropism
    • Ability of virus to replicate only in certain types of cells
    • Cell must be susceptible (specific) and permissive (conductive to repr) for the virus
  5. General constraints viruses enter in host cell w/ soln
    • Viral mRNAs in competition w/ HUGE amt of cellular mRNAs for translation
    • soln: produce abundant amounts of proteins, some degrade host mRNAs
    • Differentiated cells may not contain DNA polymerase enzymes
    • soln: DNA viruses push differentiated cells back into the cell cycle
  6. What is CPE w/ brief desc
    • Cytopathic effects
    • Virus-infected cells in culture may show CPE (diagnostic tool)
    • various physical changes, including formation of inclusion bodies
  7. 6 barriers that a virus must overcome to cause disease (general)
    • Entrance barriers
    • Cellular entrance barriers
    • Replication within the host (IFs)
    • Barriers to spreading within the host
    • Barriers to exiting the host
    • Barriers to transmission to a new host
  8. First line of defense against viral infections w/ brief description
    • Interferon:┬áreleased by infected cell
    • promotes anti-viral protein production by neighboring cells
    • increases NK cell activity
  9. Three types of infection by a virus
    • Acute: incubation, disease, convalescent
    • Latent: virus produced at intervals (repeating acute-like symptoms)
    • no infectious virus is found between episodes
    • Chronic: significant period of incubation followed by prolonged disease state (no convalescence)
  10. Disneyland
    • Measles
    • Early 2015
    • 125 cases from this outbreak (15 out of state)
    • 45% unvaccinated, 43% unknown
    • 67% unvaccinated due to belief
    • Type B3 - identical to Philippines outbreak 2014
    • Source unknown, likely international tourist
  11. Yosemite
    • Hantavirus (Sin Nombre virus)
    • Buyaviridae family
    • Carried by deer mice
    • Late 2012
    • 10 cases HPS (hantavirus pulmonary syndrome)
    • 3 dead
    • Linked to Sig. Tent Cabins
    • Cabins found to have rodent nests/tunnels in insulation, area had high trap rate, 14% catches positive for Sin Nombre
    • Infection via inhalation of infectious feces/urine
    • Park notified former visitors and future visitors were given detailed information
    • Sig. Tent Cabins dismantled
  12. Basic HIV structure
    • Sphere
    • Core has 2 copies ssRNA, reverse transcriptase
    • Capsid
    • Outer envelope
  13. HIV replication steps
    • gp120 binds to CD4 antigen (T-helper, M0, monocyte, dendritic cell, etc)
    • Chemokine receptors (normally recruit WBCs) required as co-receptors for HIV entry
    • Membranes merge, viral particle exposed in cytoplasm
    • Reverse transcriptase converts vRNA -> vDNA
    • vDNA integrated into genome (provirus)
    • ***latency can occur
    • cytokines/Ag binding causes cellular transcription
    • Viral proteins/assembly
    • Budding
    • Reinfection
  14. MAJOR HIV proteins w/ location
    • p24 in nucleocapsid
    • gp160 (precursor) -> gp120, gp41
    • gp120 in membrane (knobs/spikes)
    • gp40 is transmembrane (attaches to gp120)
    • p66, 51 in core, enzymes for reverse trans.
  15. What is Kaposi's Sarcoma
    • rare cancer caused by HHV type 8
    • Only in immuno-deficient
    • this + CMV + PCP (pneumocystis cariniii pneumonia) + candida in early AIDS patients
  16. blood/fluids vs mother-to-fetus
    • parenteral: blood/fluids
    • perinatal: mother-to-fetus
  17. How is HIV transmitted?
    • Sexual contact (most common)
    • Parenteral (IV drugs use, transfusion, needlestick)
    • Perinatal (placenta, birth, breastfeeding)
  18. Three stages of HIV infection w/ info
    • Acute infection: viremia (flu-like)
    • initial burst
    • immune response, but elimination not complete
    • Latent period: clinical latency
    • harder to detect BUT
    • virus still reproducing in spleen and lymph nodes
    • latently infected cells produce no MHC-I complexes
    • Clinical AIDS: CD4+ T cells <200uL/mL
    • Immune system falls apart
  19. define seroconversion
    time when specific Abs are made and become detectable
  20. Types of HIV testing w/ main methods
    • CD4+ T cell enumeration: flow cytometry
    • **Ab detection: ELISA screening, Western Blot confirmatory (p24,gp41,gp120/160)
    • Ag detection: testing for p24
    • *Viral nucleic acid testing: RT-PCR, r bDNA
    • looks for "viral load"
  21. Major types of hepatitis and method of transmission
    • A & E: enterically transmitted (fecal-oral)
    • naked
    • B,C,D: parenterally transmitted (fluids)
    • enveloped
  22. Hep A basic info
    • Self-limiting, no chronic disease
    • Typically resolves in a few weeks/months
    • Fecal-oral transmission (contaminated food/water)
    • naked virus (resistant to detergents,solvents, etc)
    • HAV vaccine exists, now routine
    • Blood tests for ALT, AST
    • Viral antibodies anti HAV IgM
    • Viral genetic material RT-PCR
    • **Hep E is is similar, but causes more severe illness
  23. Hep B basic info
    • Major cause of morbidity and mortality
    • Acute symptoms similar to HAV + joint pain
    • 5-10% develop chronic hepatitis, can lead to cirrhosis and liver cancer
    • vaccine available
    • MOST adults recover in 6 mos and gain immunity
    • partially double stranded DNA (uses reverse transcriptase)
    • **HDV requires HBV for infection, can be coinfection or superinfection
  24. Heb B antigens
    • HBsAg: 1st to appear
    • peaks during acute
    • ACUTE - undetectable by 4-6mo
    • CHRONIC - reamins elevated for 6+ mo
    • HbeAg: present during active replication (indicates contagious)
    • ***anti-HBs indicates recovery/protection - NOT PRODUCED DURING CHRONIC INFECTION
  25. Hep C basic info
    • progress to chronic liver disease in 85%! (most dangerous)
    • High mutation rate (persistence, lack of vaccine)
    • similar symptoms as HBV
    • 80% have no acute symptoms! (silent epidemic)
    • serum ALT and/or HCV vRNA
    • *SEROLOGICAL TESTING UNRELIABLE (takes up to 3 mos to become +)
  26. Influenza basic info
    • Droplet transmission (nasopharynx, tracheobronchial tree)
    • cilia destroyed as virus replicates (2* infections)
    • Shedding begins BEFORE symptoms
    • Nasal swab (eeeek!) for virus, then immunity
    • No proofreading = High mutation = antigenic determinant changes = escape from vaccines
  27. antigenic drift vs shift
    • drift: minor changes (point mutations)
    • shift: major changes (re-assortment of segments)
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316935
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CLS02 - Viruses
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CLS02 - Viruses
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