Research
Analysis of hemagglutinin-mediated entry tropism of H5N1 avian influenza
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* Corresponding author: Lijun Rong lijun@uic.edu
- † Equal contributors
1 Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
2 Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China
3 Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, PR China
4 College of Life Sciences, Nankai University, Tianjin 300071, PR China
5 State Key Laboratory of Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing 100730, PR China
6 National Institute for Viral Disease and Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, PR China
7 Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
Virology Journal 2009, 6:39 doi:10.1186/1743-422X-6-39
Published: 2 April 2009Abstract
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 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.
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 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.
Conclusion
Our results suggest that a host factor(s), which is yet to be identified, is required for H5N1 entry in the host cells.