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Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with Gram-positive respiratory pathogens.
- Source :
-
Journal of virology [J Virol] 2012 Sep; Vol. 86 (17), pp. 9035-43. Date of Electronic Publication: 2012 Jun 06. - Publication Year :
- 2012
-
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.
- Subjects :
- Amino Acid Motifs
Amino Acid Sequence
Animals
Cell Line
Female
Humans
Influenza A Virus, H1N1 Subtype chemistry
Influenza A Virus, H1N1 Subtype genetics
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Orthomyxoviridae Infections virology
Swine
Swine Diseases virology
Viral Proteins chemistry
Viral Proteins genetics
Influenza A Virus, H1N1 Subtype metabolism
Influenza, Human microbiology
Influenza, Human virology
Staphylococcus aureus physiology
Streptococcus physiology
Superinfection microbiology
Superinfection virology
Viral Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 86
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 22674997
- Full Text :
- https://doi.org/10.1128/JVI.00369-12