BTN3A3 evasion promotes the zoonotic potential of influenza A viruses.

Autor: Pinto RM; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.; The Roslin Institute, University of Edinburgh, Edinburgh, UK., Bakshi S; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Lytras S; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Zakaria MK; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Swingler S; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Worrell JC; School of Infection and Immunity, University of Glasgow, Glasgow, UK., Herder V; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Hargrave KE; School of Infection and Immunity, University of Glasgow, Glasgow, UK., Varjak M; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.; Faculty of Science and Technology, Institute of Technology, University of Tartu, Tartu, Estonia., Cameron-Ruiz N; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Collados Rodriguez M; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Varela M; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Wickenhagen A; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Loney C; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Pei Y; Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada., Hughes J; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Valette E; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Turnbull ML; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Furnon W; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Gu Q; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Orr L; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Taggart A; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Diebold O; The Roslin Institute, University of Edinburgh, Edinburgh, UK., Davis C; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Boutell C; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Grey F; The Roslin Institute, University of Edinburgh, Edinburgh, UK., Hutchinson E; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Digard P; The Roslin Institute, University of Edinburgh, Edinburgh, UK., Monne I; Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Legnaro, Italy., Wootton SK; Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada., MacLeod MKL; School of Infection and Immunity, University of Glasgow, Glasgow, UK., Wilson SJ; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Palmarini M; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK. massimo.palmarini@glasgow.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Jul; Vol. 619 (7969), pp. 338-347. Date of Electronic Publication: 2023 Jun 28.
DOI: 10.1038/s41586-023-06261-8
Abstrakt: Spillover events of avian influenza A viruses (IAVs) to humans could represent the first step in a future pandemic 1 . Several factors that limit the transmission and replication of avian IAVs in mammals have been identified. There are several gaps in our understanding to predict which virus lineages are more likely to cross the species barrier and cause disease in humans 1 . Here, we identified human BTN3A3 (butyrophilin subfamily 3 member A3) 2 as a potent inhibitor of avian IAVs but not human IAVs. We determined that BTN3A3 is expressed in human airways and its antiviral activity evolved in primates. We show that BTN3A3 restriction acts primarily at the early stages of the virus life cycle by inhibiting avian IAV RNA replication. We identified residue 313 in the viral nucleoprotein (NP) as the genetic determinant of BTN3A3 sensitivity (313F or, rarely, 313L in avian viruses) or evasion (313Y or 313V in human viruses). However, avian IAV serotypes, such as H7 and H9, that spilled over into humans also evade BTN3A3 restriction. In these cases, BTN3A3 evasion is due to substitutions (N, H or Q) in NP residue 52 that is adjacent to residue 313 in the NP structure 3 . Thus, sensitivity or resistance to BTN3A3 is another factor to consider in the risk assessment of the zoonotic potential of avian influenza viruses.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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