Influenza

• Influenza virus

  Enveloped virus with segmented genome (n=8)
• Influenza viruses mainly cause respiratory and non-respiratory symptoms in humans
• Quintus Ennius: 'I never indulge in rhyme or stanza Unless I'm in bed with the influenza'
• Virus

  Simple, miniscule, infectious, obligate intracellular parasite (only reproduce within living cell) comprising of genetic material (DNA or RNA) surrounded by a protein coat and/or an envelope derived from a host cell membrane
• Host range


  Limited range of animals which can be infected
• Antagonize


  Viruses have to antagonize the strong immune system of animals to be able to cause disease
• Structure of influenza A virion

  • Mainly Spherical
  • Enveloped
  • ssRNA (-) sense
  • Replication in the nucleus
  • Segmented genome (n=8)
• Haemagglutinin (HA)

  • Binds sialic acid receptors -> viral entry
  • Agglutinates RBCs
  • Antigenic (neutralizing)
• Neuraminidase (NA)


  • Cleaves sialic acid to release virus
  • Degrades mucin
  • Antigenic (non-neutralizing)
• Matrix protein 2 (M2)

  • Forms proton channel that facilitates uncoating and assembly
  • Stabilizes the virus budding
  • Antigenic (neutralizing)
• Outer Lipid Envelope

  • Lipid bilayer from plasma membrane of infected host cell
  • Supported by the M1 protein, which play role in virion assembly
• Nucleocapsid


  • Each of eight different single stranded RNA + nucleoprotein (NP) + RNA polymerase (PB1, PB2 and PA)
• Types of Influenza Viruses

  • Influenza A
  • Influenza B
  • Influenza C
  • Influenza D
• Epidemic


  Rapid spread of infection in a city, state or entire country over a short period of time
• Pandemic


  An epidemic that spreads across boarders, even worldwide, affecting large numbers
• Antigenic Structure and Classification

  • H (Haemagglutinin)
  • N (Neuraminidase)
  • Strain (subtype) specific antigen
• Influenza Pandemics

  • Spanish Flu, 1918 (A/H1N1, 50 million deaths)
  • Asian Flu, 1957-58 (H2N2, 1.5-2 million deaths)
  • Hong Kong Flu, 1968-69 (H3N2, 1 million deaths)
  • Swine Flu, 2009 (novel H1N1, over 18209 deaths)
• Influenza Virus Replication Cycle

  1. Attachment

  2. Uncoating

  3. Transcription

  4. Replication

  5. Assembly

  6. Budding
• Haemagglutinin (HA)

  • Exists as trimer in influenza virion
  • Receptor Binding site - confers host-specificity
  • Cleavage site - where the single chain is cut into two chains. At the N-terminus it is fusion peptide which is critical for infectivity
• Receptor specificity of influenza viruses

  • Human viruses preferentially bind to α2,6-linked SA
  • Avian viruses preferentially bind to α2,3-linked SA
  • Swine can act a mixing vessel
• Animals especially birds play important roles in influenza virus emergence
• Why do we Continue to have Influenza Virus Epidemics/Pandemics?

  1. Antigenic shift - major changes due to a re-assortment of genes that occurs when two different influenza viruses infect the same host

  2. Antigenic drift - minor changes in the antigenic sites of the HA and NA, because of error prone replication and no proofreading
• Influenza A viruses Prevalent in Human

  • A/California/7/2009 (H1N1)
  • A/Victoria/361/2011 (H3N2)
  • B/Massachusetts/2/2012-like
• How vaccine strains are selected?

  100 National Influenza Centers -> 5 WHO Collaborating Centers -> Recommend vaccine twice a year -> Each country make their own selection for next year vaccination
• Adamantanes

  • Amantadine and Rimantadine are M2-ion channel inhibitors
  • Blocks viral uncoating
  • Treatment or Prophylaxis
  • Influenza A only
  • CNS + anticholinergic effect, teratogenic
  • Strains are developing resistance
• Neuraminidase inhibitors

  • Oseltamivir and Zanamavir
  • Influenza A+B
  • Generally well-tolerated, some nausea/vomit
  • Most effective within 48h of onset
  • Relief from symptoms for ~1-2 days or less
  • Treatment or prophylaxis (oseltamivir)
  • Oral or inhaled (zanamavir)
• T/F The nucleocapsid of the influenza virus contains eight single strands of RNA and RNA polymerase?

  True
• T/F Haemagglutinin and neuraminidase are surface glycoproteins of influenza A virus?

  True
• T/F Influenza virus replicates in cytoplasm?

  false
• Structure of viron contains what?

  Haemagglutinin, Neuraminidase, Matrix protein 2
• Envelope and interior contains: outer lipid envelope, nucleocapsid
• what is a serotype?

  different types according to internal structure proteins which cant cross-react
• Who does influenza A affect?

  Humans, swine, birds, horse, bats, dogs
• who does influenza B affect?

  humans, seals
• who does influenza C affect?

  human, swine, dogs
• who does influenza D affect?

  swine, cattle
• which serotype of influenza produces mild or asymptomatic infections?

  C
• Which serotype of influenza is most capable unleashing epidemic and pandemics?

  A
• How are influenza viruses named?

  specific HA and NA subtypes
• how many haemagglutinin types are there?

  18