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

文献类型： 外文期刊

第一作者： Fatima, Urooj

作者： Fatima, Urooj;Zhang, Zhenyu;Zhang, Haili;Wang, Xue-Feng;Xu, Ling;Chu, Xiaoyu;Ji, Shuang;Wang, Xiaojun;Ji, Shuang

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关键词： MxA; equine Mx1; influenza A viruses; polymerase activity; interspecies transmission; nucleoprotein; equine influenza

期刊名称：VIRUSES-BASEL （ 影响因子：5.048； 五年影响因子：5.127 ）

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年卷期： 2019 年 11 卷 12 期

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收录情况： SCI

摘要： 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 (H3N8(JL89)) and A/chicken/Zhejiang/DTID-ZJU01/2013 (H7N9(ZJ13)) that confer eqMx1 resistance and sensitivity respectively. A substantial reduction in Mx1 resistance was observed for the two mutations G34S and H52N in H3N8(JL89) 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.

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