Analysis of hemagglutinin-mediated entry tropism of H5N1 avian influenza

Virol J. 2009 Apr 2:6:39. doi: 10.1186/1743-422X-6-39.

Abstract

Background: Avian influenza virus H5N1 is a major concern as a potential global pandemic. It is thought that multiple key events must take place before efficient human-to-human transmission of the virus occurs. The first step in overcoming host restriction is viral entry which is mediated by HA, responsible for both viral attachment and viral/host membrane fusion. HA binds to glycans-containing receptors with terminal sialic acid (SA). It has been shown that avian influenza viruses preferentially bind to alpha2,3-linked SAs, while human influenza A viruses exhibit a preference for alpha2,6-linked SAs. Thus it is believed the precise linkage of SAs on the target cells dictate host tropism of the viruses.

Results: We demonstrate that H5N1 HA/HIV pseudovirus can efficiently transduce several human cell lines including human lung cells. Interestingly, using a lectin binding assay we show that the presence of both alpha2,6-linked and alpha2,3-linked SAs on the target cells does not always correlate with efficient transduction. Further, HA substitutions of the residues implicated in switching SA-binding between avian and human species did not drastically affect HA-mediated transduction of the target cells or target cell binding.

Conclusion: Our results suggest that a host factor(s), which is yet to be identified, is required for H5N1 entry in the host cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Ammonium Chloride / pharmacology
  • Animals
  • Birds
  • CHO Cells
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • DNA Mutational Analysis
  • Enzyme Inhibitors / pharmacology
  • HIV / physiology
  • HeLa Cells
  • Hemagglutinins / metabolism*
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Influenza A Virus, H5N1 Subtype / physiology*
  • Influenza in Birds / virology*
  • Jurkat Cells
  • Macrolides / pharmacology
  • Mice
  • Neuraminidase / pharmacology
  • Protein Binding
  • Protein Structure, Tertiary / genetics
  • Recombinant Proteins / metabolism
  • Sialic Acids / analysis
  • Tropism*
  • Vero Cells
  • Virus Internalization* / drug effects

Substances

  • Enzyme Inhibitors
  • Hemagglutinins
  • Macrolides
  • Recombinant Proteins
  • Sialic Acids
  • Ammonium Chloride
  • bafilomycin A1
  • Neuraminidase