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Open AccessArticle

Equine Mx1 Restricts Influenza A Virus Replication by Targeting at Distinct Site of its Nucleoprotein

1
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
2
Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(12), 1114; https://doi.org/10.3390/v11121114
Received: 25 September 2019 / Revised: 25 November 2019 / Accepted: 29 November 2019 / Published: 2 December 2019
(This article belongs to the Special Issue Equine Viruses)
Interferon-mediated host factors myxovirus (Mx) proteins are key features in regulating influenza A virus (IAV) infections. Viral polymerases are essential for viral replication. The Mx1 protein has been known to interact with viral nucleoprotein (NP) and PB2, resulting in the influence of polymerase activity and providing interspecies restriction. The equine influenza virus has evolved as an independent lineage to influenza viruses from other species. We estimated the differences in antiviral activities between human MxA (huMxA) and equine Mx1 (eqMx1) against a broad range of IAV strains. We found that huMxA has antiviral potential against IAV strains from non-human species, whereas eqMx1 could only inhibit the polymerase activity of non-equine species. Here, we demonstrated that NP is the main target of eqMx1. Subsequently, we found adaptive mutations in the NP of strains A/equine/Jilin/1/1989 (H3N8JL89) and A/chicken/Zhejiang/DTID-ZJU01/2013 (H7N9ZJ13) that confer eqMx1 resistance and sensitivity respectively. A substantial reduction in Mx1 resistance was observed for the two mutations G34S and H52N in H3N8JL89 NP. Thus, eqMx1 is an important dynamic force in IAV nucleoprotein evolution. We, therefore, suggest that the amino acids responsible for Mx1 resistance should be regarded as a robust indicator for the pandemic potential of lately evolving IAVs.
Keywords: MxA; equine Mx1; influenza A viruses; polymerase activity; interspecies transmission; nucleoprotein; equine influenza MxA; equine Mx1; influenza A viruses; polymerase activity; interspecies transmission; nucleoprotein; equine influenza
MDPI and ACS Style

Fatima, U.; Zhang, Z.; Zhang, H.; Wang, X.-F.; Xu, L.; Chu, X.; Ji, S.; Wang, X. Equine Mx1 Restricts Influenza A Virus Replication by Targeting at Distinct Site of its Nucleoprotein. Viruses 2019, 11, 1114.

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