tetano
Editor, Senior Moderator
PLoS One. 2013 Jun 14;8(6):e67616. doi: 10.1371/journal.pone.0067616. Print 2013.
Asparagine Substitution at PB2 Residue 701 Enhances the Replication, Pathogenicity, and Transmission of the 2009 Pandemic H1N1 Influenza A Virus.
Zhou B, Pearce MB, Li Y, Wang J, Mason RJ, Tumpey TM, Wentworth DE.
Source
J. Craig Venter Institute, Rockville, Maryland, United States of America ; Wadsworth Center, New York State Department of Health, Albany, New York, United States of America ; Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York, United States of America.
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.
PMID:
23799150
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/23799150
Asparagine Substitution at PB2 Residue 701 Enhances the Replication, Pathogenicity, and Transmission of the 2009 Pandemic H1N1 Influenza A Virus.
Zhou B, Pearce MB, Li Y, Wang J, Mason RJ, Tumpey TM, Wentworth DE.
Source
J. Craig Venter Institute, Rockville, Maryland, United States of America ; Wadsworth Center, New York State Department of Health, Albany, New York, United States of America ; Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York, United States of America.
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.
PMID:
23799150
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/23799150