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Asparagine Substitution at PB2 Residue 701 Enhances the Replication, Pathogenicity, and Transmission of the 2009 Pandemic H1N1 Influenza A Virus

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Title
Asparagine Substitution at PB2 Residue 701 Enhances the Replication, Pathogenicity, and Transmission of the 2009 Pandemic H1N1 Influenza A Virus
Published in
PLOS ONE, June 2013
DOI 10.1371/journal.pone.0067616
Pubmed ID
Authors

Bin Zhou, Melissa B. Pearce, Yan Li, Jieru Wang, Robert J. Mason, Terrence M. Tumpey, David E. Wentworth

Abstract

The 2009/2010 pandemic influenza virus (H1N1pdm) contains an avian-lineage PB2 gene that lacks E627K and D701N substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. Previous studies have shown that PB2-627K is not necessary because of a compensatory Q591R substitution. The role that PB2-701N plays in the H1N1pdm phenotype is not well understood. Therefore, PB2-D701N was introduced into an H1N1pdm virus (A/New York/1682/2009 (NY1682)) and analyzed in vitro and in vivo. Mini-genome replication assay, in vitro replication characteristics in cell lines, and analysis in the mouse and ferret models demonstrated that PB2-D701N increased virus replication rates and resulted in more severe pathogenicity in mice and more efficient transmission in ferrets. In addition, compared to the NY1682-WT virus, the NY1682-D701N mutant virus induced less IFN-λ and replicated to a higher titer in primary human alveolar epithelial cells. These findings suggest that the acquisition of the PB2-701N substitution by H1N1pdm viruses may result in more severe disease or increase transmission in humans.

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The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Unknown 33 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 29%
Researcher 10 29%
Student > Bachelor 3 9%
Student > Master 3 9%
Lecturer 1 3%
Other 5 15%
Unknown 2 6%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 24%
Agricultural and Biological Sciences 7 21%
Immunology and Microbiology 6 18%
Veterinary Science and Veterinary Medicine 3 9%
Medicine and Dentistry 2 6%
Other 3 9%
Unknown 5 15%