Resp Virus.txt

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emm64
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141689
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Resp Virus.txt
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2012-03-15 00:18:08
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Resp Virus Lung
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Resp Virus Lung
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  1. Common colds virii
    • 30-50% - Rhinoviruses (Picorna-)
    • 10-30% - Coronaviruses
    • 10-15% - Adenoviruses
    • Caused by 200+ types of viruses
    • No vaccines
    • No anti-viral drug
    • continuous 3+ billion cost per year
    • annual frequencty decreases with age
  2. Picornaviruses
    • - non-enveloped
    • - ss (+)RNA genome, IRES
    • Both Rhino- and Entero- can be causes for common colds but Rhino is much more common.
  3. Enterovirus
    • picornavirus
    • Acid resistant
    • 37C optimum growth temp
    • oral-fecal transmission
    • gut primary infection site
  4. Rhinovirus
    • Picornavirus
    • Labile Acid sensitivity
    • 33C optimum temp
    • aerosol and fomites(contaminated objects) transmission
    • wash hands
    • respiratory tract primary
    • antibody only good for 1 type (of >100)
    • no anti ddrug
  5. Coronaviruses
    • (+) RNA genome
    • Enveloped
    • Human coronaviruses
    • - 1/3 of common cold
    • SARS
    • no vaccine or anti-corona
  6. Lower Respiratory Virii
  7. SARS
    • 2002 South China
    • A new syndrome observed in late 2002 in southern China
    • June, 2003 - 8,000 cases worldwide and 775 deaths
    • Last outbreak was in 2004 from laboratory
    • quarantine travelers w fever
    • 1/3 of original cases came from food handlers
    • A closely related coronavirus was found in bats
    • Directly transmit to humans, evolve in humans to
    • facilitate human-to-human transmission
  8. Adenoviruses
    • dsDNA genome
    • non-enveloped
    • first recognized among military recruits during 1950-60 (World War II)
    • Since 1999, 10-12% of recruits became infected.
    • Transmission through via respiratory droplets and fecal matter
    • Most immunocompetent patients have a full recovery
    • Most are asymptomatic.
    • Most people have been infected with at least 1 type by age 15
    • Oral vaccine of live attenuated adenoviruses was used since 1971, but discontinued in late 1990
    • Oral vaccine of type 4 and 7 in FDA approval review
    • No anti-adeno drugs
  9. Paramyxoviruses
    • (-) RNA genome
    • Enveloped
    • Fusion protein (syncytia)
    • Attachment protein
    • Parainfluenza viruses (type 1-4)
    • Respiratory syncytial virus (RSV)
    • Major cause of severe respiratory infection in infants and young children (<3 year-old="" br="">Asymptomatic in most cases
    • mild-cold like symptoms (upper respiratory tract)
    • - older children and adults
    • Complications
    • bronchitis/bronchiolitis in young children
    • 1st cause for Croup (laryngotracheobronchitis)
    • - swelling at the voice box, “barking” cough
    • No antiviral drug/No vaccine
  10. Croup
    • laryngotracheobronchitis
    • Paramyxovirus 1st cause
    • swelling at the voice box, “barking” cough
  11. RSV
    • Respiratory Syncytial virus
    • Milder symptoms in older children and adults
    • Complications
    • Bronchiolitis/bronchitis in young children
    • 1st cause for Infantile bronchiolitis/pneumonia
    • 100,000 hospitalizations, 4,500 deaths/year in US
    • 1st cause for fatal respiratory tract infection in infants
    • Diagnosis-Rapid detection of RSV antigen from nasopharyngeal aspirates.
    • Antiviral drugs
    • Ribavirin – anti-viral RNA polymerase, used only in persons at high risk for severe disease (premature and immunocompromised infants)
    • Passive immunization (high risk groups)
    • RespiGam – pooled human serum containing anti-RSV antibody
    • Synagis – antibody against F protein of RSV
  12. RSV Therapies
    • Antiviral drugs
    • Ribavirin – anti-viral RNA polymerase, used only in persons at high risk for severe disease (premature and immunocompromised infants)
    • Passive immunization (high risk groups)
    • RespiGam – pooled human serum containing anti-RSV antibody
    • Synagis – antibody against F protein of RSV
  13. Flu Pandemics
    • 1918-19 Spanish Flu (H1N1)
    • 20-50 million deaths worldwide
    • >500,000 U.S. deaths
    • Less deadly as time goes on
    • 2009 (H1N1)
    • < 20,000 deaths
    • pandemic resulting from subtypes of hemagglutinin neuraminidase
    • come from birds(natural resevoir) many more strains that may become human
    • pigs/human infection both ways and can recombine(genetic reassortment)
  14. Influenza virus
    • (-)RNA, 8 segments
    • enveloped
    • HA – attachment
    • NA – virion release
    • M2 – uncoating
    • Three types
    • A (mammals and birds)
    • B (mammals)
    • C (mammals)
  15. Life cycle of influenza viruses
    • RNA replication in the nucleus
    • The HA has several functions:
    • viral attachment protein, binding to sialic acid on epithelial cell surface receptors
    • promotes fusion of the envelope to the cell membrane;
    • hemagglutinates red blood cells
    • The proton channel formed by the M2 protein promotes acidification of the envelope contents to break the protein-protein interactions to allow uncoating and delivery of the nucleocapsid into the cytoplasm.
    • -other RNA viruses replicate in the cytoplasm;
    • in contrast, influenza goes into the nucleus
    • -virus attaches to cell surface via hemagglutinin, then uses endosomal pathway;
    • it exits endosome using the M2 protein > genetic material is released, which enters nucleus
    • -for this particle to be released, you need neuraminade at surface- so virus can be released to infect other cells
  16. Pathogenesis of influenza viruses


    • virus first targets and kills mucus-secreting, ciliated, and other epithelial cells, causing the loss of this primary defense system.
    • NA facilitates the development of the infection by cleaving sialic acid residues of the mucus, thereby providing access to tissue.
    • If the virus spreads to the lower respiratory tract, the infection can cause severe desquamation (shedding) of bronchial or alveolar epithelium down to a single-cell basal layer or to the basement membrane.
    • In addition to compromising the natural defenses of the respiratory tract, influenza infection promotes bacterial adhesion to the epithelial cells.
    • Pneumonia may result from a viral pathogenesis or from a secondary bacterial infection.
    • Influenza may also cause a transient or low-level viremia but rarely involves tissues other than the lung.
    • -how does virus cause disease? It comes in through aerosol inoculation, entering & replicating in respiratory tract; in respiratory tract, it kills cells, so that there is temporary dysfunction; the immune response is stimulated to fight against viral infection- depending on how fast viral replication & immune response is, there may or may not be symptoms at this point; sometimes, the virus travels into the lower respiratory tract to cause pneumonia; when the virus is replicating and killing cells in the respiratory tract, you also make it more vulnerable to bacterial infection- dysfunction due to infection causes loss of ability to fight bacterial infection; in rare cases, viruses spread to blood, which spreads the virus to other organs (causing complications, ex. in brain)
  17. Complications of Flu
    • 36,000 deaths/year US high risk elderly (>65 years)
    • Pneumonia (elderly, young, immunocomp)
    • 1. viral
    • 2. bacterial
    • Non-pulmonary
    • -CNS(young)
    • -cardiac (myocarditis/pericarditis) (old)
  18. anti-flu immunity
    • anti-HA antibody -but flu evolves (antigen drift)
    • flu-specific cytotoxic lymphocytes(T-cells)
  19. antigen drift
    • errors during RNA replication
    •  Minor changes in HA/NA
    •  the pre-existing antibody does not work
    •  outbreak occurs
    • continuous process
    •  vaccine strains must be updated
    • Direct transmission of
    • animal influenza A to
    • humans
    • Genetic reassortment
    • (gene swapping)
    •  Major changes in HA/NA
    •  pandemics occurs
    • (new, spreading globally, but not necessarily deadly)
  20. Flu Nomenclature
    • virus type,
    • geographic origin
    • strain number- sometimes not present
    • year of isolation
    • virus subtype
  21. Influenza vaccine
    • Killed virus (grown in eggs)-> Ab only
    • - short-lived protective effects
    • - need to decide which strain to use by February
    • A/Brisbane/10/2007 (H3N2)
    • A/Brisbane/59/2007 (H1N1)
    • B/Florida/4/2006
    • Live attenuated (cold-adapted, grown in eggs)-> Ab and CTL(cytotoxic lymphocytes)
    • - limited in upper tract
    • - FluMist (nasal spray)
    • - mucosal immunity
    • - only to healthy individuals
    • -could provide spectrum (blanket) protection
  22. Anti-influenza drugs
  23. Human H5N1 cases
    • example of different pathologies- different rate of killing, different timelines
    • rare, contact with sick/dead poultry
    • deadly
    • rare man-to-man transmission
    • little immunity for humans

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