Adaptive mutation in influenza A virus non-structural gene is linked to host switching and induces a novel protein by alternative splicing

FieldValue
dc.contributor.authorSelman, Mohammed
dc.contributor.authorDankar, Samar K
dc.contributor.authorForbes, Nicole E
dc.contributor.authorJia, Jian-Jun
dc.contributor.authorBrown, Earl G
dc.date.accessioned2012-11-28T15:05:58Z
dc.date.available2012-11-28T15:05:58Z
dc.date.created2012
dc.date.issued2012-11-28
dc.identifier.citationEmerging Microbes & Infections (2012) 1, e42; doi:10.1038/emi.2012.38 Published online 21 November 2012
dc.identifier.urihttp://hdl.handle.net/10393/23547
dc.identifier.urihttp://www.nature.com/emi/journal/v1/n11/full/emi201238a.html
dc.description.abstractLittle is known about the processes that enable influenza A viruses to jump into new host species. Here we show that the non-structural protein1 nucleotide substitution, A374G, encoding the D125G(GATGGT) mutation, which evolved during the adaptation of a human virus within a mouse host, activates a novel donor splice site in the non-structural gene, hence producing a novel influenza A viral protein, NS3. Using synonymous 125G mutations that do not activate the novel donor splice site, NS3 was shown to provide replicative gain-of-function. The protein sequence of NS3 is similar to NS1 protein but with an internal deletion of a motif comprised of three antiparallel β-strands spanning codons 126 to 168 in NS1. The NS1-125G(GGT) codon was also found in 33 natural influenza A viruses that were strongly associated with switching from avian to mammalian hosts, including human, swine and canine populations. In addition to the experimental human to mouse switch, the NS1-125G(GGT) codon was selected on avian to human transmission of the 1997 H5N1 and 1999 H9N2 lineages, as well as the avian to swine jump of 1979 H1N1 Eurasian swine influenza viruses, linking the NS1 125G(GGT) codon with host adaptation and switching among multiple species.
dc.description.sponsorshipThis project has been supported by the CIHR Pandemic Preparedness Team grant to the CIHR Canadian Influenza Pathogenesis Team TPA-90188, and CIHR operating grant MOP-74526.
dc.subjectinfluenza A virus
dc.subjectnon-structural protein 1
dc.subjectNS gene
dc.subjectNS3
dc.subjectNS1
dc.subjectviral splicing
dc.subjecthost switch
dc.titleAdaptive mutation in influenza A virus non-structural gene is linked to host switching and induces a novel protein by alternative splicing
dc.typeArticle
dc.identifier.doi10.1038/emi.2012.38
CollectionBiochimie, microbiologie et immunologie // Biochemistry, Microbiology and Immunology

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