tetano
Editor, Senior Moderator
Virology. 2014 Sep 3;468-470C:207-213. doi: 10.1016/j.virol.2014.08.010. [Epub ahead of print]
PB2-E627K and PA-T97I substitutions enhance polymerase activity and confer a virulent phenotype to an H6N1 avian influenza virus in mice.
Cheng K1, Yu Z2, Chai H3, Sun W4, Xin Y4, Zhang Q5, Huang J4, Zhang K4, Li X4, Yang S4, Wang T4, Zheng X4, Wang H4, Qin C6, Qian J4, Chen H5, Hua Y7, Gao Y8, Xia X9.
Author information
Abstract
H6N1 avian influenza viruses (AIVs) may pose a potential human risk as suggested by the first documented naturally-acquired human H6N1 virus infection in 2013. Here, we set out to elucidate viral determinants critical to the pathogenesis of this virus using a mouse model. We found that the recombinant H6N1 viruses possessing both the PA-T97I and PB2-E627K substitutions displayed the greatest enhancement of replication in vitro and in vivo. Polymerase complexes possessing either PB2-E627K, PA-T97I, and PB2-E627K/PA-T97I displayed higher virus polymerase activity when compared to the wild-type virus, which may account for the increased replication kinetics and enhanced virulence of variant viruses. Our results demonstrate that PB2-E627K and PA-T97I enhance the ability of H6N1 virus to replicate and cause disease in mammals. Influenza surveillance efforts should include scrutiny of these regions of PB2 and PA because of their impact on the increased virulence of H6N1 AIVs in mice.
Copyright ? 2014 Elsevier Inc. All rights reserved.
KEYWORDS:
Avian influenza virus; H6N1; Mice; Pathogenicity
PMID:
25194918
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25194918
PB2-E627K and PA-T97I substitutions enhance polymerase activity and confer a virulent phenotype to an H6N1 avian influenza virus in mice.
Cheng K1, Yu Z2, Chai H3, Sun W4, Xin Y4, Zhang Q5, Huang J4, Zhang K4, Li X4, Yang S4, Wang T4, Zheng X4, Wang H4, Qin C6, Qian J4, Chen H5, Hua Y7, Gao Y8, Xia X9.
Author information
Abstract
H6N1 avian influenza viruses (AIVs) may pose a potential human risk as suggested by the first documented naturally-acquired human H6N1 virus infection in 2013. Here, we set out to elucidate viral determinants critical to the pathogenesis of this virus using a mouse model. We found that the recombinant H6N1 viruses possessing both the PA-T97I and PB2-E627K substitutions displayed the greatest enhancement of replication in vitro and in vivo. Polymerase complexes possessing either PB2-E627K, PA-T97I, and PB2-E627K/PA-T97I displayed higher virus polymerase activity when compared to the wild-type virus, which may account for the increased replication kinetics and enhanced virulence of variant viruses. Our results demonstrate that PB2-E627K and PA-T97I enhance the ability of H6N1 virus to replicate and cause disease in mammals. Influenza surveillance efforts should include scrutiny of these regions of PB2 and PA because of their impact on the increased virulence of H6N1 AIVs in mice.
Copyright ? 2014 Elsevier Inc. All rights reserved.
KEYWORDS:
Avian influenza virus; H6N1; Mice; Pathogenicity
PMID:
25194918
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25194918