title: 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.
  
  
  CONCLUSIONS
  Our results suggest that a host factor(s), which is yet to be identified, is required for H5N1 entry in the host cells.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. yingguo6@yahoo.com
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Emily
authors.initials: E
authors.lastname: Rumschlag-Booms
authors.forename: Jizhen
authors.initials: J
authors.lastname: Wang
authors.forename: Haixia
authors.initials: H
authors.lastname: Xiao
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.forename: Youjia
authors.initials: Y
authors.lastname: Cao
authors.forename: Michael
authors.initials: M
authors.lastname: Caffrey
authors.forename: Lijun
authors.initials: L
authors.lastname: Rong