Mammalian adaptation of an avian influenza A virus involves stepwise changes in NS1

Chauché, C. , Nogales, A., Zhu, H., Goldfarb, D., Shanizza A.I., A., Gu, Q., Parrish, C.R., Martínez-Sobrido, L., Marshall, J.F. and Murcia, P.R. (2018) Mammalian adaptation of an avian influenza A virus involves stepwise changes in NS1. Journal of Virology, 92(5), e01875-17. (doi:10.1128/JVI.01875-17) (PMID:29237841) (PMCID:PMC5809720)

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Abstract

Influenza A viruses (IAVs) are common pathogens of birds that occasionally establish endemic infections in mammals. The processes and mechanisms that result in IAV mammalian adaptation are poorly understood. The viral non-structural 1 (NS1) protein counteracts the interferon (IFN) response, a central component of the host-species barrier. We characterised the NS1 proteins of equine influenza virus (EIV), a mammalian IAV lineage of avian origin. We showed that evolutionary distinct NS1s counteract the IFN response using different and mutually exclusive mechanisms: while the NS1s of early EIVs block general gene expression by binding to the cellular polyadenylation specific factor 30 (CPSF30), NS1s from more evolved EIVs specifically block the induction of IFN-stimulated genes by interfering with the JAK/STAT pathway. These contrasting anti-IFN strategies are associated with two mutations that appeared sequentially and became rapidly selected during EIV evolution, highlighting the importance of evolutionary processes on immune evasion mechanisms during IAV adaptation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Chauche, Dr Caroline and Gu, Dr Quan and Goldfarb, Daniel Max and Marshall, Dr John and Murcia, Dr Pablo
Authors: Chauché, C., Nogales, A., Zhu, H., Goldfarb, D., Shanizza A.I., A., Gu, Q., Parrish, C.R., Martínez-Sobrido, L., Marshall, J.F., and Murcia, P.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:13 December 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of Virology 92(5):e01875-17
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
709011Quinquennial Core FundsMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/9MVLS III - CENTRE FOR VIRUS RESEARCH