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Modification of the hemagglutinin cleavage site allows indirect activation of avian influenza virus H9N2 by bacterial staphylokinase.

Abstract
Influenza H9N2 is considered to be a low pathogenicity avian influenza (LPAI) virus that commonly infects avian species and can also infect humans. In 1996, the influenza virus, A/chicken/Korea/MS96-CE6/1996/H9N2 (MS96) was isolated from an outbreak in multiple farms in South Korea that resulted in upwards of 30% mortality in infected chickens, with the virus infecting a number of extrapulmonary tissues, indicating internal spread. However, in experimental infections, complete recovery of specific pathogen free (SPF) chickens occurred. Such a discrepancy indicated an alternative pathway for MS96 virus to gain virulence in farmed chickens. A key determinant of influenza pathogenesis is the susceptibility of the viral hemagglutinin (HA) to proteolytic cleavage/activation. Here, we identified that an amino acid substitution, Ser to Tyr found at the P2 position of the MS96 HA cleavage site optimizes cleavage by the protease plasmin (Pm). Importantly, we identified that certain Staphylococcus sp. are able to cleave and activate MS96 HA by activating plasminogen (Plg) to plasmin by use of a virulence factor, staphylokinase. Overall, these studies provide an in-vitro mechanism for bacterially mediated enhancement of influenza activation, and allow insight into the microbiological mechanisms underlying the avian influenza H9N2 outbreak in Korea in1996.
AuthorsLongping V Tse, Gary R Whittaker
JournalVirology (Virology) Vol. 482 Pg. 1-8 (Aug 2015) ISSN: 1096-0341 [Electronic] United States
PMID25841078 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Fibrinolysin
  • Metalloendopeptidases
  • auR protein, Staphylococcus aureus
Topics
  • Animals
  • Chickens
  • Disease Outbreaks
  • Fibrinolysin (metabolism)
  • Hemagglutinin Glycoproteins, Influenza Virus (genetics, metabolism)
  • Influenza A Virus, H9N2 Subtype (drug effects, genetics, isolation & purification)
  • Influenza in Birds (epidemiology, virology)
  • Korea
  • Metalloendopeptidases (metabolism)
  • Microbial Interactions
  • Mutation, Missense
  • Virulence

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