[Source: Journal of Virology, full page: (LINK). Abstract, edited.]
A Novel Activation Mechanism of Avian Influenza Virus H9N2 by Furin
Longping V. Tsea,b, Alice M. Hamiltona, Tamar Frilinga and Gary R. Whittakera,b
Author Affiliations: aDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA bNew York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester, New York, USA
Published ahead of print 20 November 2013, doi: 10.1128/JVI.02648-13 J. Virol. February 2014 vol. 88 no. 3 1673-1683
Avian influenza virus H9N2 is prevalent in waterfowl and has become endemic in poultry in Asia and the Middle East. H9N2 influenza viruses have served as a reservoir of internal genes for other avian influenza viruses that infect humans, and several cases of human infection by H9N2 influenza viruses have indicated its pandemic potential. Fortunately, an extensive surveillance program enables close monitoring of H9N2 influenza viruses worldwide and has generated a large repository of virus sequences and phylogenetic information. Despite the large quantity of sequences in different databases, very little is known about specific virus isolates and their pathogenesis. Here, we characterize a low-pathogenicity avian influenza virus, A/chicken/Israel/810/2001 (H9N2) (Israel810), which is representative of influenza virus strains that have caused severe morbidity and mortality in poultry farms. We show that under certain circumstances the Israel810 hemagglutinin (HA) can be activated by furin, a hallmark of highly pathogenic avian influenza virus. We demonstrate that Israel810 HA can be cleaved in cells with high levels of furin expression and that a mutation that eliminates a glycosylation site in HA1 allows the Israel810 HA to gain universal cleavage in cell culture. Pseudoparticles generated from Israel810 HA, or the glycosylation mutant, transduce cells efficiently. In contrast, introduction of a polybasic cleavage site into Israel810 HA leads to pseudoviruses that are compromised for transduction. Our data indicate a mechanism for an H9N2 evolutionary pathway that may allow it to gain virulence in a distinct manner from H5 and H7 influenza viruses.
Received 12 September 2013. Accepted 12 November 2013.
Address correspondence to Gary R. Whittaker, firstname.lastname@example.org.
Published ahead of print 20 November 2013
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