Equine Mx1 Restricts Influenza A Virus Replication by Targeting at Distinct Site of its Nucleoprotein.
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.
['Fatima|Urooj|U|', 'Zhang|Zhenyu|Z|', 'Zhang|Haili|H|', 'Wang|Xue-Feng|XF|', 'Xu|Ling|L|', 'Chu|Xiaoyu|X|', 'Ji|Shuang|S|', 'Wang|Xiaojun|X|']
D000818:Animals D004285:Dogs D019143:Evolution, Molecular D057809:HEK293 Cells D006734:Horse Diseases D006736:Horses D054884:Host-Pathogen Interactions D006801:Humans D009980:Influenza A virus D007251:Influenza, Human D061985:Madin Darby Canine Kidney Cells D009154:Mutation D064547:Myxovirus Resistance Proteins D019590:Nucleocapsid Proteins D009976:Orthomyxoviridae Infections D010802:Phylogeny D011485:Protein Binding D016601:RNA-Binding Proteins D013045:Species Specificity D014758:Viral Core Proteins D014779:Virus Replication
equine Mx1 nucleoprotein polymerase activity equine influenza MxA influenza A viruses interspecies transmission