Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

Hassan Zaraket, Tatiana Baranovich, Bryan S. Kaplan, Robert Carter, Min-Suk Song, James C. Paulson, Jerold E. Rehg, Justin Bahl, Jeri C. Crumpton, Jon Seiler, Michael Edmonson, Gang Wu, Erik Karlsson, Thomas Fabrizio, Huachen Zhu, Yi Guan, Matloob Husain, Stacey Schultz-Cherry, Scott Krauss, Ryan McBride, Robert G. Webster, Elena A. Govorkova, Jinghui Zhang, Charles J. Russell and Richard J. Webby ()
Additional contact information
Hassan Zaraket: St Jude Children’s Research Hospital
Tatiana Baranovich: St Jude Children’s Research Hospital
Bryan S. Kaplan: St Jude Children’s Research Hospital
Robert Carter: St Jude Children’s Research Hospital
Min-Suk Song: St Jude Children’s Research Hospital
James C. Paulson: The Scripps Research Institute
Jerold E. Rehg: St Jude Children’s Research Hospital
Justin Bahl: School of Public Health, The University of Texas Health Science Center at Houston
Jeri C. Crumpton: St Jude Children’s Research Hospital
Jon Seiler: St Jude Children’s Research Hospital
Michael Edmonson: St Jude Children’s Research Hospital
Gang Wu: St Jude Children’s Research Hospital
Erik Karlsson: St Jude Children’s Research Hospital
Thomas Fabrizio: St Jude Children’s Research Hospital
Huachen Zhu: Joint Influenza Research Center (Shantou University Medical College & Hong Kong University), Shantou University Medical College
Yi Guan: Joint Influenza Research Center (Shantou University Medical College & Hong Kong University), Shantou University Medical College
Matloob Husain: University of Otago
Stacey Schultz-Cherry: St Jude Children’s Research Hospital
Scott Krauss: St Jude Children’s Research Hospital
Ryan McBride: The Scripps Research Institute
Robert G. Webster: St Jude Children’s Research Hospital
Elena A. Govorkova: St Jude Children’s Research Hospital
Jinghui Zhang: St Jude Children’s Research Hospital
Charles J. Russell: St Jude Children’s Research Hospital
Richard J. Webby: St Jude Children’s Research Hospital

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness.

Date: 2015
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DOI: 10.1038/ncomms7553

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