Rapid emergence of a PB2-E627K substitution confers a virulent phenotype to an H9N2 avian influenza virus during adoption in mice

Archives of Virology
Xiaoyu SangXianzhu Xia

Abstract

The worldwide circulation of H9N2 avian influenza virus in poultry, the greater than 2.3 % positive rate for anti-H9 antibodies in poultry-exposed workers, and several reports of human infection indicate that H9N2 virus is a potential threat to human health. Here, we found three mutations that conferred high virulence to H9N2 virus in mice after four passages. The PB2-E627K substitution rapidly appeared at the second passage and played a decisive role in virulence. Polymerase complexes possessing PB2-E627K displayed 16.1-fold higher viral polymerase activity when compared to the wild-type virus, which may account for enhanced virulence of this virus. The other two substitutions (HA-N313D and HA-N496S) enhanced binding to both α2,3-linked and α2,6-linked sialic acid receptors; however, the HA-N313D and N496S substitutions alone decreased the virulence of mouse-adapted virus. Furthermore, this mouse-adapted virus was still not transmissible among guinea pigs by direct contact (0/3 pairs). Our findings show that adaption in mice enhanced the viral polymerase activity and receptor-binding ability, which resulted in a virulent phenotype in mice but not a transmissible phenotype in guinea pigs, indicating that host factors play an im...Continue Reading

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Citations

May 14, 2019·The Journal of General Virology·Guanlong XuJiabo Ding
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·Silvia Carnaccini, Daniel R Perez
Oct 3, 2017·Frontiers in Microbiology·Chunmao ZhangJun Qian
Oct 12, 2018·Emerging Microbes & Infections·Runfeng LiZifeng Yang
Jul 1, 2017·Archives of Virology·Jeong-Hyun NamJeong-Ki Kim
Nov 13, 2015·The Journal of General Virology·Hanna SediriHans-Dieter Klenk

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