Analysis of hemagglutinin-mediated entry tropism of H5N1 avian influenza

• Main Authors: Gao George F, Guo Li, Wang Jianwei, Yu Jia, Xiao Haixia, Wang Jizhen, Rumschlag-Booms Emily, Guo Ying, Cao Youjia, Caffrey Michael, Rong Lijun
• Format: Article
• Language: English
• Published: BMC 2009-04-01
• Series: Virology Journal
• Online Access: http://www.virologyj.com/content/6/1/39

<p>Abstract</p> <p>Background</p> <p>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 α2,3-linked SAs, while human influenza A viruses exhibit a preference for α2,6-linked SAs. Thus it is believed the precise linkage of SAs on the target cells dictate host tropism of the viruses.</p> <p>Results</p> <p>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 α2,6-linked and α2,3-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.</p> <p>Conclusion</p> <p>Our results suggest that a host factor(s), which is yet to be identified, is required for H5N1 entry in the host cells.</p>