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

Loading next page...
Springer Vienna
Copyright © 2015 by Springer-Verlag Wien
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
Publisher site
See Article on Publisher Site


  • 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
  • Seroprevalence of avian influenza H9N2 among poultry workers in Shandong Province, China
    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
  • Experimental infection of non-human primates with avian influenza virus (H9N2)
    Zhang, K; Xu, W; Zhang, Z; Wang, T; Sang, X; Cheng, K; Yu, Z; Zheng, X; Wang, H; Zhao, Y; Huang, G; Yang, S; Qin, C; Gao, Y; Xia, X
  • 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
  • Detection of expression of influenza virus receptors in tissues of BALB/c mice by histochemistry
    Ning, ZY; Luo, MY; Qi, WB; Yu, B; Jiao, PR; Liao, M

You’re reading a free preview. Subscribe to read the entire article.

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches


Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.



billed annually
Start Free Trial

14-day Free Trial