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

Rapid emergence of a PB2-E627K substitution confers a virulent phenotype to an H9N2 avian... 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 important role in adaptive evolution of influenza in new hosts. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

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

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Publisher
Springer Vienna
Copyright
Copyright © 2015 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2383-5
Publisher site
See Article on Publisher Site

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 important role in adaptive evolution of influenza in new hosts.

Journal

Archives of VirologySpringer Journals

Published: May 1, 2015

References

  • Domestic cats and dogs are susceptible to H9N2 avian influenza virus
    Zhang, K; Zhang, Z; Yu, Z; Li, L; Cheng, K; Wang, T; Huang, G; Yang, S; Zhao, Y; Feng, N; Fu, J; Qin, C; Gao, Y; Xia, X
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    Huang, R; Wang, AR; Liu, ZH; Liang, W; Li, XX; Tang, YJ; Miao, ZM; Chai, TJ
  • The origin of the PB1 segment of swine influenza A virus subtype H1N2 determines viral pathogenicity in mice
    Metreveli, G; Gao, Q; Mena, I; Schmolke, M; Berg, M; Albrecht, RA; Garcia-Sastre, A
  • Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets
    Imai, M; Watanabe, T; Hatta, M; Das, SC; Ozawa, M; Shinya, K; Zhong, G; Hanson, A; Katsura, H; Watanabe, S; Li, C; Kawakami, E; Yamada, S; Kiso, M; Suzuki, Y; Maher, EA; Neumann, G; Kawaoka, Y
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  • Mutations in PA, NP, and HA of a pandemic (H1N1) 2009 influenza virus contribute to its adaptation to mice
    Sakabe, S; Ozawa, M; Takano, R; Iwastuki-Horimoto, K; Kawaoka, Y
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    Ning, ZY; Luo, MY; Qi, WB; Yu, B; Jiao, PR; Liao, M

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