The Role of the B-Allele of the Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity

Matthew Turnbull, Helen Wise, Marlynne Nicol, Nikki Smith, Rebecca L Dunfee, Philippa Beard, Brett W Jagger, Yvonne Ligertwood, Gareth Hardisty, Haixia Xiao, Donald J Benton, Alice M Coburn, Joao A Paulo, Steven P Gygi, John W McCauley, Jeffery K. Taubenberger, Samantha Lycett, Michael P Weekes, Bernadette Dutia, Paul Digard

Research output: Contribution to journalArticlepeer-review

Abstract

Two ‘alleles' of segment 8 (NS) circulate in non-chiropteran influenza A viruses. The A-allele is found in avian and mammalian viruses, but the B-allele is viewed as almost exclusively avian. This might reflect that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian NS segments were introduced into human H1N1 and H3N2 viruses. In no case was peak virus titre substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titres in mice, although the avian segment 8s reduced weight-loss compared to the PR8 parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian NS segments provoked lower expression of IFN-stimulated genes in cells than the WT. Thus, neither A- nor B-alleles of avian virus-derived NS segments necessarily attenuate virus replication in a mammalian host although they can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian-derived A-allele into mammals compared to 6 introductions of a B-allele. However, A-allele isolates from birds outnumber B-allele samples and the relative rates of Aves to Mammalia transmission are not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B-allele being especially restricted is misleading – with implications in the assessment of pandemic potential of avian influenza viruses.
Original languageEnglish
Pages (from-to)9263-9284
JournalJournal of Virology
Volume90
Issue number20
Early online date3 Aug 2016
DOIs
Publication statusPublished - 29 Sep 2016

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