Role of the B allele of the influenza A virus segment 8 in setting mammalian host range and pathogenicity

Turnbull, M. L. et al. (2016) Role of the B allele of the influenza A virus segment 8 in setting mammalian host range and pathogenicity. Journal of Virology, 90(20), pp. 9263-9284. (doi: 10.1128/JVI.01205-16) (PMID:27489273) (PMCID:PMC5044859)

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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.

Item Type:Articles
Additional Information:This work was supported by grants from the Biotechnology and Biological Sciences Research Council ( (BB/ J004324/1 to P.D., P.M.B., S.J.L., H.M.W., and B.M.D.) and the Medical Research Council ( (MR/K000276/1 to P.D.) and in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, to J.K.T. M.P.W. is supported by a Wellcome Trust Senior Clinical Fellowship ( (108070/Z/15/Z). M.L.T. is supported by a Biotechnology and Biological Sciences Research Council EastBio Ph.D. studentship ( (BB/J01446X/1). S.J.L. is supported by a University of Edinburgh Chancellor’s Fellowship.
Glasgow Author(s) Enlighten ID:Turnbull, Dr Matthew and Lycett, Dr Samantha
Authors: Turnbull, M. L., Wise, H. M., Nicol, M. Q., Smith, N., Dunfee, R. L., Beard, P. M., Jagger, B. W., Ligertwood, Y., Hardisty, G. R., Xiao, H., Benton, D. J., Coburn, A. M., Paulo, J. A., Gygi, S. P., McCauley, J. W., Taubenberger, J. K., Lycett, S. J., Weekes, M. P., Dutia, B. M., and Digard, P.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN (Online):1098-5514
Published Online:03 August 2016
Copyright Holders:Copyright © 2016 Turnbull et al.
First Published:First published in Journal of Virology 90(20):9263-9284
Publisher Policy:Reproduced under a Creative Commons License

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