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A PB1 T296R substitution enhance polymerase activity and confer a virulent phenotype to a 2009 pandemic H1N1 influenza virus in mice.
- Source :
-
Virology . Dec2015, Vol. 486, p180-186. 7p. - Publication Year :
- 2015
-
Abstract
- While the 2009 pandemic H1N1 virus has become established in the human population as a seasonal influenza virus, continued adaptation may alter viral virulence. Here, we passaged a 2009 pandemic H1N1 virus (A/Changchun/01/2009) in mice. Serial passage in mice generated viral variants with increased virulence. Adapted variants displayed enhanced replication kinetics in vitro and vivo . Analysis of the variants genomes revealed 6 amino acid changes in the PB1 (T296R), PA (I94V), HA (H3 numbering; N159D, D225G, and R226Q), and NP (D375N). Using reverse genetics, we found that a PB1-T296R substitution found in all adapted viral variants enhanced viral replication kinetics in vitro and vivo , increased viral polymerase activity in human cells, and was sufficient for enhanced virulence of the 2009 pandemic H1N1 virus in mice. Therefore, we defined a novel influenza pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 486
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 111301822
- Full Text :
- https://doi.org/10.1016/j.virol.2015.09.014