Title |
Asparagine Substitution at PB2 Residue 701 Enhances the Replication, Pathogenicity, and Transmission of the 2009 Pandemic H1N1 Influenza A Virus
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Published in |
PLOS ONE, June 2013
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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. |
X Demographics
Geographical breakdown
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United States | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
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United Kingdom | 1 | 3% |
Unknown | 33 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 10 | 29% |
Researcher | 10 | 29% |
Student > Bachelor | 3 | 9% |
Student > Master | 3 | 9% |
Lecturer | 1 | 3% |
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Unknown | 2 | 6% |
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Medicine and Dentistry | 2 | 6% |
Other | 3 | 9% |
Unknown | 5 | 15% |