Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with gram-positive respiratory pathogens

Jenni N. Weeks-Gorospe, Heather R. Hurtig, Amy R. Iverson, Margaret J. Schuneman, Richard J. Webby, Jonathan A. McCullers, Victor C. Huber

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A combination of viral, bacterial, and host factors contributes to the severity and overall mortality associated with influenza virus-bacterium superinfections. To date, the virulence associated with the recently identified influenza virus protein PB1-F2 has been largely defined using models of primary influenza virus infection, with only limited assessment in models of Streptococcus pneumoniae superinfection. Specifically, these studies have incorporated isogenic viruses that differ in the PB1-F2 expressed, but there is still knowledge to be gained from evaluation of natural variants derived from a nonhuman host species (swine). Using this rationale, we developed the hypothesis that naturally occurring viruses expressing variants of genes, like the PB1-F2 gene, can be associated with the severity of secondary bacterial infections. To test this hypothesis, we selected viruses expressing variants in PB1-F2 and evaluated outcomes from superinfection with three distinct Gram-positive respiratory pathogens: Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes. Our results demonstrate that the amino acid residues 62L, 66S, 75R, 79R, and 82L, previously proposed as molecular signatures of PB1-F2 virulence for influenza viruses in the setting of bacterial superinfection, are broadly associated with enhanced pathogenicity in swine in a bacterium-specific manner. Furthermore, truncated PB1-F2 proteins can preferentially increase mortality when associated with Streptococcus pyogenes superinfection. These findings support efforts to increase influenza virus surveillance to consider viral genotypes that could be used to predict increased severity of superinfections with specific Gram-positive respiratory pathogens.

Original languageEnglish (US)
Pages (from-to)9035-9043
Number of pages9
JournalJournal of Virology
Volume86
Issue number17
DOIs
StatePublished - Sep 1 2012

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swine influenza
Superinfection
Influenza A virus
Orthomyxoviridae
Swine
Phenotype
phenotype
pathogens
Streptococcus pyogenes
Virulence
Streptococcus pneumoniae
Viruses
viruses
virulence
Bacteria
swine
Mortality
bacteria
Virus Diseases
bacterial infections

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with gram-positive respiratory pathogens. / Weeks-Gorospe, Jenni N.; Hurtig, Heather R.; Iverson, Amy R.; Schuneman, Margaret J.; Webby, Richard J.; McCullers, Jonathan A.; Huber, Victor C.

In: Journal of Virology, Vol. 86, No. 17, 01.09.2012, p. 9035-9043.

Research output: Contribution to journalArticle

Weeks-Gorospe, Jenni N. ; Hurtig, Heather R. ; Iverson, Amy R. ; Schuneman, Margaret J. ; Webby, Richard J. ; McCullers, Jonathan A. ; Huber, Victor C. / Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with gram-positive respiratory pathogens. In: Journal of Virology. 2012 ; Vol. 86, No. 17. pp. 9035-9043.
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