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Basic Characteristics of Mutations
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Mutation Site
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M105K |
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Mutation Site Sentence
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We show that three mutations in particular occur with high frequency in the viral nucleoprotein (NP) protein (G102R, M105K and D375N) in a specific structural area upon in vivo adaptation. |
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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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NP |
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Standardized Encoding Gene
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NP
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Genotype/Subtype
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H1N1 |
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Viral Reference
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HQ104928.1;HQ104926.1;HQ104924.1;HM598305.1;HQ104929.1;HQ104927.1;HQ104925.1;GU480807.1
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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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Y |
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Target Gene
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KPNA4
KPNA2
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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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- |
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Location
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- |
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Literature Information
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PMID
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31044563
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Title
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Alternative interaction sites in the influenza A virus nucleoprotein mediate viral escape from the importin-alpha7 mediated nuclear import pathway
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Author
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Resa-Infante P,Bonet J,Thiele S,Alawi M,Stanelle-Bertram S,Tuku B,Beck S,Oliva B,Gabriel G
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Journal
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The FEBS journal
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Journal Info
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2019 Sep;286(17):3374-3388
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Abstract
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Influenza A viruses are able to adapt to restrictive conditions due to their high mutation rates. Importin-alpha7 is a component of the nuclear import machinery required for avian-mammalian adaptation and replicative fitness in human cells. Here, we elucidate the mechanisms by which influenza A viruses may escape replicative restriction in the absence of importin-alpha7. To address this question, we assessed viral evolution in mice lacking the importin-alpha7 gene. We show that three mutations in particular occur with high frequency in the viral nucleoprotein (NP) protein (G102R, M105K and D375N) in a specific structural area upon in vivo adaptation. Moreover, our findings suggest that the adaptive NP mutations mediate viral escape from importin-alpha7 requirement likely due to the utilization of alternative interaction sites in NP beyond the classical nuclear localization signal. However, viral escape from importin-alpha7 by mutations in NP is, at least in part, associated with reduced viral replication highlighting the crucial contribution of importin-alpha7 to replicative fitness in human cells.
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Sequence Data
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PRJEB32637
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