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

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.

journal_name

Virology

journal_title

Virology

authors

Wörmann X,Lesch M,Welke RW,Okonechnikov K,Abdurishid M,Sieben C,Geissner A,Brinkmann V,Kastner M,Karner A,Zhu R,Hinterdorfer P,Anish C,Seeberger PH,Herrmann A,Meyer TF,Karlas A

doi

10.1016/j.virol.2016.02.002

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

118-29

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(16)00045-3

journal_volume

492

pub_type

杂志文章

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