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define variolation
Inhale (inoculate) dried crust from infected pox to produce immunity
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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
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General steps in viral replication
- Attachment
- Entry
- Uncoating
- Transcription
- Translation
- Replication
- Assembly
- Release
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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
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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
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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
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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
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First line of defense against viral infections w/ brief description
- Interferon: released by infected cell
- promotes anti-viral protein production by neighboring cells
- increases NK cell activity
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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)
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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
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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
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Basic HIV structure
- Sphere
- Core has 2 copies ssRNA, reverse transcriptase
- Capsid
- Outer envelope
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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
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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.
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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
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blood/fluids vs mother-to-fetus
- parenteral: blood/fluids
- perinatal: mother-to-fetus
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How is HIV transmitted?
- Sexual contact (most common)
- Parenteral (IV drugs use, transfusion, needlestick)
- Perinatal (placenta, birth, breastfeeding)
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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
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define seroconversion
time when specific Abs are made and become detectable
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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"
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Major types of hepatitis and method of transmission
- A & E: enterically transmitted (fecal-oral)
- naked
- B,C,D: parenterally transmitted (fluids)
- enveloped
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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
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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
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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
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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 +)
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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
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antigenic drift vs shift
- drift: minor changes (point mutations)
- shift: major changes (re-assortment of segments)
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