Analysis of hemagglutinin-mediated entry tropism of H5N1 avian influenza.

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.

• Authors: Ying Guo, Emily Rumschlag-Booms, Jizhen Wang, Haixia Xiao, Jia Yu, Jianwei Wang, Li Guo, George F Gao, Youjia Cao, Michael Caffrey, Lijun Rong
• Journal: Virology journal (Virol J) Vol. 6 Pg. 39 (Apr 02 2009) ISSN: 1743-422X [Electronic] England
• PMID: 19341465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)