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Basic Characteristics of Mutations
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Mutation Site
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D130E |
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Mutation Site Sentence
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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. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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HA |
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Standardized Encoding Gene
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HA
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Genotype/Subtype
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H1N1 |
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Viral Reference
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GQ166207; GQ166209; GQ166211; GQ166213; GQ166215;GQ166217; GQ166219; GQ166221
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Functional Impact and Mechanisms
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Disease
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Influenza A
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Immune
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- |
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Target Gene
|
-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
|
- |
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Location
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Germany |
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Literature Information
|
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PMID
|
26914510
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Title
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Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells
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Author
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Wormann 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
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Journal
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Virology
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Journal Info
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2016 May;492:118-29
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Abstract
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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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Sequence Data
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-
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