Adaptive amino acid substitutions enhance the virulence of an H7N7 avian influenza virus isolated from wild waterfowl in mice

Veterinary Microbiology
Qiang ChenYuping Hua

Abstract

Although H7N7 AIVs primarily circulate in wild waterfowl, documented cases of human infection with H7N7 viruses suggest they may pose a pandemic threat. Here, we generated mouse-adapted variants of a wild waterfowl-origin H7N7 virus to identify adaptive changes that confer enhanced virulence in mammals. The mouse lethal doses (MLD50) of the adapted variants were reduced >5000-fold compared to the parental virus. Mouse-adapted variants viruses displayed enhanced replication in vitro and in vivo, and acquired the ability to replicate in extrapulmonary tissues. These observations suggest that enhanced growth characteristics and modified cell tropism may increase the virulence of H7N7 AIVs in mice. Genomic analysis of the adapted variant viruses revealed amino acid changes in the PB2 (E627K), PB1 (R118I), PA (L550M), HA (G214R), and NA (S372N) proteins. Our results suggest that these amino acid substitutions collaboratively enhance the ability of H7N7 virus to replicate and cause severe disease in mammals.

References

Mar 1, 1992·Microbiological Reviews·R G WebsterY Kawaoka
May 22, 2002·Journal of Virology·Terrence M TumpeyDavid E Swayne
Dec 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·G GabrielJ Stech
May 18, 2006·Emerging Infectious Diseases·Thaweesak SongsermYong Poovorawan
Sep 9, 2008·Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc·Erica SpackmanDavid E Stallknecht
Feb 7, 2013·Physical Review Letters·M AblikimUNKNOWN BESIII Collaboration
Feb 14, 2013·Avian Diseases·Brigita SlavecOlga Zorman-Rojs
Mar 6, 2013·Virus Research·Jessica A Belser, Terrence M Tumpey
Apr 13, 2013·The New England Journal of Medicine·Rongbao GaoYuelong Shu
Apr 23, 2013·Virus Research·Kun ZhangXianzhu Xia
May 7, 2013·Lancet·Marc Van Ranst, Philippe Lemey
May 15, 2013·Archives of Virology·Kun ZhangXianzhu Xia
Jun 5, 2013·Virus Research·Gülsah GabrielHans-Dieter Klenk
Jul 19, 2013·Journal of Virology·Ji-Young MinKanta Subbarao
Apr 11, 2014·Archives of Virology·Kaihui ChengHongliang Chai
Jun 6, 2014·Journal of Virology·Volker Czudai-MatwichHans-Dieter Klenk
Jun 13, 2014·Journal of Virology·Jessica A BelserTerrence M Tumpey
Jul 20, 2014·Veterinary Microbiology·Qunhui LiXiufan Liu

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Citations

Oct 3, 2017·Frontiers in Microbiology·Chunmao ZhangJun Qian
Jul 29, 2017·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Haibo WuNanping Wu
Nov 9, 2021·Frontiers in Veterinary Science·Xueyun LiYuelong Shu

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