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

Xenia Wörmann, Markus Lesch, Robert-William Welke, Konstantin Okonechnikov, Mirshat Abdurishid, Christian Sieben, Andreas Geissner, Volker Brinkmann, Markus Kastner, Andreas Karner, Rong Zhu, Peter Hinterdorfer, Chakkumkal Anish, Peter H. Seeberger, Andreas Herrmann, Thomas F. Meyer, Alexander Karlas

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5 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)118-129
Number of pages12
JournalVirology
Volume492
DOIs
Publication statusPublished - 1 May 2016

Keywords

  • A/Hamburg/04/2009
  • Hemagglutinin
  • High-throughput sequencing
  • Reverse genetics
  • Viral adaptation

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