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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.

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.

journal_name

Virology

journal_title

Virology

authors

Yu Z,Cheng K,Sun W,Zhang X,Li Y,Wang T,Wang H,Zhang Q,Xin Y,Xue L,Zhang K,Huang J,Yang S,Qin C,Wilker PR,Yue D,Chen H,Gao Y,Xia X

doi

10.1016/j.virol.2015.09.014

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

180-6

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(15)00405-5

journal_volume

486

pub_type

杂志文章

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