Analysis of hemagglutinin-mediated entry tropism of H5N1 avian influenza.
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.
Guo
Ying
Y
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. yingguo6@yahoo.com
Rumschlag-Booms
Emily
E
Wang
Jizhen
J
Xiao
Haixia
H
Yu
Jia
J
Wang
Jianwei
J
Guo
Li
L
Gao
George F
GF
Cao
Youjia
Y
Caffrey
Michael
M
Rong
Lijun
L