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Lecture 7

IMM250 Lecture 7 - Influenza.docx

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Liliana Clemenza

IMM250 Lecture 7 Emerging Influenza Variants and the case for improved vaccines March 13, 2013 Smallpox eradication by vaccination has been effective. Deaths have dramatically subsided. Smallpox eradicated by a WHO campaign, 1979. Polio is the next WHO target. Problem diseases – lack effective vaccine  HIV  Tuberculosis  Malaria  Influenza Virus The “flu”  Infection with Influenza virus  An acute upper respiratory infection  Not a mild cold – rapid onset, often bed-ridden for a few days, fever, cough and severe muscle aches.  “Stomach flu” is caused by other viruses, NOT Influenza virus. Spread of Influenza  Virus starts replicating in lung epithelium.  Flu is more prevalent in winter. Tested guinea pigs: virus is more readily transmitted under cool dry conditions. At higher humidity and temperature, droplets are larger and settle faster, need more direct contact. Under cooler, drier conditions can spread through air. Virus also inactivated faster at higher temperatures. Types of Influenza Viruses  Influenza A – regular outbreaks  Influenza B – sporadic outbreaks  Influenza C – common but seldom causes disease Orthomyxoviruses (family of RNA viruses)  Pleomorphic (the envelope can occur in spherical and filamentous forms)  Influenza types A, B, C  Febrile (symptoms of fever), respiratory illness with systemic symptoms.  Different variants within strains. Influenza Virus – negative strand RNA virus  Enveloped-sheathed in lipid bilayer  8 RNA segments  HA hemagglutinin (H1-16) o H1, H2, H3 – human strains o H5N1 – current “bird flu” o Binds to cells, allows entry.  NA – neuraminidase (N1-9) IMM250 Lecture 7 Emerging Influenza Variants and the case for improved vaccines March 13, 2013 o Needed to get out of cells  M – Matrix – M1, M2  NP – nucleoprotein  NS – nonstructural  PS,PB1, PB2 – RNA polymerase How influenza infects cells  Virus HA (hemagglutinin) attaches to terminal sialic acids on surface carbohydrates.  Endocytosis of virus, in endosome o Acidic pH: HA (hemagglutinin) changes conformation to cause virus envelope fusion with endosome membrane and release of viral contents into cytosol. o Uncoating removes viral envelope, releasing viral nucleic acid (RNA). o Viral RNA enters nucleus .  Cleavage of newly synthesized HA (hemagglutinin) by enzyme in lung epithelial cells, but not other cells restricts site of virus activity to human lung. Avian – more systemic infection.  Release (via budding) of newly synthesized viral particles requires N (neuraminidase) to release sialic acid. The reservoir of influenza viruses  Viruses can be transmitted from birds or pigs.  Human adapted: h1N1, H3N2  H2N2 is no longer circulating in humans. Two kinds of variation in influenza 1. Antigenic Shift  2 strains of flu infect the same animal  Re-assortment of RNA segments from the two strains can give rise to a new virus  E.g. “New” H1N1, 2009. 2. Antigenic Drift  Influenza RNA polymerase makes copies of its RNA to make new viruses, but it is very error prone – frequent mutations arise – lead to rapid evolution of viruses.  Anti-Influenza drugs: problems with drugs – resistant variants rapidly emerge.  Need to use drugs early before virus replicates extensively (First 2-3 days of infection)
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