Swine influenza virus PA and neuraminidase gene reassortment into human H1N1iInfluenza Virus is associated with an altered pathogenic phenotype linked to increased MIP-2 expression

Dlugolenski, Daniel, Jones, Les, Howerth, Elizabeth, Wentworth, David, Tompkins, S. Mark and Tripp, Ralph A. 2015, Swine influenza virus PA and neuraminidase gene reassortment into human H1N1iInfluenza Virus is associated with an altered pathogenic phenotype linked to increased MIP-2 expression, Journal of virology, vol. 89, no. 10, pp. 5651-5667, doi: 10.1128/JVI.00087-15.

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Title Swine influenza virus PA and neuraminidase gene reassortment into human H1N1iInfluenza Virus is associated with an altered pathogenic phenotype linked to increased MIP-2 expression
Author(s) Dlugolenski, Daniel
Jones, Les
Howerth, Elizabeth
Wentworth, David
Tompkins, S. Mark
Tripp, Ralph A.
Journal name Journal of virology
Volume number 89
Issue number 10
Start page 5651
End page 5667
Total pages 17
Publisher American Society for Microbiology
Place of publication Washington, D.C.
Publication date 2015-05
ISSN 1098-5514
Keyword(s) amino acid sequence
animals
cell line
chemokine CXCL2
cytokines
female
hemagglutinin Glycoproteins
immunity
influenza A Virus, H1N1 Subtype
Influenza Virus
killer cells
lung
lymphocyte activation
mice
molecular sequence data
neuraminidase
neutrophil infiltration
orthomyxoviridae Infections
phenotype
RNA replicase
reassortant vruses
sequence homology
amino acid
swine diseases
T-Lymphocytes
viral proteins
virulence
inbred BALB C
influenza A Virus, H1N2 Subtype
Summary Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. IMPORTANCE: Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.
Language eng
DOI 10.1128/JVI.00087-15
Field of Research 110199 Medical Biochemistry and Metabolomics not elsewhere classified
07 Agricultural And Veterinary Sciences
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, American Society For Microbology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30082012

Document type: Journal Article
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School of Medicine
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