Influenza A Virus Notes

Influenza A Virus

Prevalence and Transmission

  • Influenza A is a common, life-threatening virus in the U.S.
  • Infects approximately 10% of the U.S. population annually.
  • Causes about 20,000 deaths per year.
  • Transmitted through droplets or aerosols from sneezes or coughs of infected individuals.
  • Inhalation of droplets allows the virus to invade host cells.

Viral Structure

  • Contains a genome of single-stranded RNA segments.
  • Includes enzymes for viral replication within the host cell.
  • Encased in a shell of matrix proteins.
  • Has a phospholipid envelope with embedded proteins, including hemagglutinin (H).
  • Hemagglutinin (H) is crucial for viral cell entry.

Hemagglutinin and Host Cell Binding

  • Influenza virus binds to host cell receptor proteins containing polysaccharides that terminate with sialic acid.
  • Sialic acid attached to galactose acts as a recognition site for the hemagglutinin protein.
  • Alpha-2-3 linkage:
    • Sialic acid connects to galactose at the number two carbon of sialic acid and the number three carbon of galactose.
    • Avian influenza strain H5N1 recognizes this linkage.
    • Found mainly in birds.
    • In humans, these carbohydrates are located deep within the lungs.
    • This may be why H5N1 is deadly but rarely transmitted between humans.
  • Alpha-2-6 linkage:
    • Found mainly in the upper respiratory tract of humans.
    • Human influenza A viruses bind to these receptors.

Hemagglutinin Complex

  • Consists of a trimer of subunits.
  • Each subunit includes a domain that passes through the viral envelope and a domain that binds to sialic acid receptors on the host cell.

Hemagglutinin Cleavage and Activation

  • Hemagglutinin must be cleaved to make the virus infective.
  • An enzyme from the epithelial lining of the human respiratory tract performs this cleavage.
  • Cleavage releases one end of a segment called a fusion peptide.
  • The fusion peptide is hydrophobic and buried within the core of the hemagglutinin trimeric complex.

Viral Entry and Fusion

  • Host cell takes up the virus via endocytosis.
  • The endocytic vesicle fuses with a lysosome and its interior acidifies.
  • Lowered pH induces a conformational change.
    • Shifts the receptor binding region back.
    • Triggers the fusion peptides forward to penetrate the vesicle membrane.
  • Multiple trimeric hemagglutinin molecules mediate fusion between viral and host membranes.
  • The fusion process expels the contents of the virus into the host cytoplasm.

Replication Cycle

  • Once inside the host cytoplasm, the virus begins its replication cycle.