Analysis of hemagglutinin-mediated entry tropism of H5N1 avian influenza

• Published in: Virology journal 2009-04, Vol.6 (39), p.39-39, Article 39
• Main Authors: Guo, Ying, Rumschlag-Booms, Emily, Wang, Jizhen, Xiao, Haixia, Yu, Jia, Wang, Jianwei, Guo, Li, Gao, George F, Cao, Youjia, Caffrey, Michael, Rong, Lijun
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Ammonium Chloride - pharmacology; Animals; Avian influenza; Avian influenza virus; Birds; Cell Line; Cercopithecus aethiops; CHO Cells; COS Cells; Cricetinae; Cricetulus; Development and progression; DNA Mutational Analysis; Enzyme Inhibitors - pharmacology; HeLa Cells; Hemagglutinins - metabolism; HIV - physiology; Host-Pathogen Interactions - drug effects; Host-virus relationships; Human immunodeficiency virus; Humans; Influenza A Virus, H5N1 Subtype - physiology; Influenza in Birds - virology; Jurkat Cells; Macrolides - pharmacology; Mice; Neuraminidase - pharmacology; Physiological aspects; Protein Binding; Protein Structure, Tertiary - genetics; Recombinant Proteins - metabolism; Sialic acids; Sialic Acids - analysis; Tropism; Vero Cells; Virus Internalization - drug effects
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-6-39

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