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  Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

Wörmann, X., Lesch, M., Welke, R.-W., Okonechnikov, K., Abdurishid, M., Sieben, C., et al. (2016). Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells. Virology, 492, 118-129. doi:10.1016/j.virol.2016.02.002.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-D188-D Version Permalink: http://hdl.handle.net/21.11116/0000-0006-59BA-5
Genre: Journal Article

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 Creators:
Wörmann, Xenia, Author
Lesch, Markus, Author
Welke, Robert-William, Author
Okonechnikov, Konstantin, Author
Abdurishid, Mirshat, Author
Sieben, Christian, Author
Geißner, Andreas1, Author              
Brinkmann, Volker, Author
Kastner, Markus, Author
Karner, Andreas, Author
Zhu, Rong, Author
Hinterdorfer, Peter, Author
Chakkumkal, Anish1, Author              
Seeberger, Peter H.2, Author              
Herrmann, Andreas, Author
Meyer, Thomas F., Author
Karlas, Alexander, Author
Affiliations:
1Chakkumal Anish, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863299              
2Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              

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Free keywords: A/Hamburg/04/2009; Hemagglutinin; High-throughput sequencing; Reverse genetics; Viral adaptation; Open Access
 Abstract: The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA1 D130E, HA2 I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production.

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 Dates: 2016-02-232016
 Publication Status: Published in print
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 Identifiers: DOI: 10.1016/j.virol.2016.02.002
BibTex Citekey: Wörmann2016118
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Title: Virology
Source Genre: Journal
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Publ. Info: Orlando, Fla. : Academic Press
Pages: - Volume / Issue: 492 Sequence Number: - Start / End Page: 118 - 129 Identifier: ISSN: 0042-6822