. doi: 10.1016/j.virs.2022.12.002
Citation: Jian Chen, Jian Liu, Zhilu Chen, Daobin Feng, Cuisong Zhu, Jun Fan, Shuye Zhang, Xiaoyan Zhang, Jianqing Xu. Nonmuscle myosin IIA promotes the internalization of influenza A virus and regulates viral polymerase activity through interacting with nucleoprotein in human pulmonary cells .VIROLOGICA SINICA, 2023, 38(1) : 128-141.  http://dx.doi.org/10.1016/j.virs.2022.12.002

肌球蛋白重链9促进甲型流感病毒进入并感染人肺脏细胞且通过与病毒核蛋白互作调节病毒聚合酶活性

  • 甲型流感病毒(Influenza A virus,IAV)造成季节性和反复流行,是对全球公共卫生造成严重威胁。鉴于IAV潜在的大流行风险,更好地了解病毒与宿主之间的相互作用并开发新的抗病毒策略变得越来越重要。在这里,我们报道了非肌肉肌球蛋白IIA(nonmuscle myosin IIA,MYH9)介导的对于IAV感染的调控。人肺上皮细胞中,敲除内源MYH9分子可以抑制病毒的结合和内吞,进而抑制IAV的有效感染。有趣的是,过表达MYH9分子也导致了病毒感染的显著降低。但是,过表达MYH9分子不影响病毒黏附、内化或脱壳的能力,而是抑制了病毒核糖核蛋白(viral ribonucleoprotein,vRNP)的生物活性。进一步实验发现,过量的MYH9分子可能通过与病毒核蛋白(nucleoprotein,NP)相互作用阻断vRNP的形成,导致细胞核内vRNP的减少,从而抑制后续病毒RNA的转录和复制。总而言之,我们发现MYH9分子可以与IAV的NP蛋白相互作用并参与vRNP复合体的调控,从而影响病毒的复制。这些发现对宿主-流感病毒相互作用的复杂界面提供了新的见解,为研究抗病毒药物提供了一个潜力的靶点。

Nonmuscle myosin IIA promotes the internalization of influenza A virus and regulates viral polymerase activity through interacting with nucleoprotein in human pulmonary cells

  • Influenza A virus (IAV), responsible for seasonal epidemics and recurring pandemics, represents a global threat to public health. Given the risk of a potential IAV pandemic, it is increasingly important to better understand virus-host interactions and develop new anti-viral strategies. Here, we reported nonmuscle myosin IIA (MYH9)-mediated regulation of IAV infection. MYH9 depletion caused a profound inhibition of IAV infection by reducing viral attachment and internalization in human lung epithelial cells. Surprisingly, overexpression of MYH9 also led to a significant reduction in viral productive infection. Interestingly, overexpression of MYH9 retained viral attachment, internalization, or uncoating, but suppressed the viral ribonucleoprotein (vRNP) activity in a minigenome system. Further analyses found that excess MYH9 might interrupt the formation of vRNP by interacting with the viral nucleoprotein (NP) and result in the reduction of the completed vRNP in the nucleus, thereby inhibiting subsequent viral RNA transcription and replication. Together, we discovered that MYH9 can interact with IAV NP protein and engage in the regulation of vRNP complexes, thereby involving viral replication. These findings enlighten new mechanistic insights into the complicated interface of host-IAV interactions, ultimately making it an attractive target for the generation of antiviral drugs.

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    Nonmuscle myosin IIA promotes the internalization of influenza A virus and regulates viral polymerase activity through interacting with nucleoprotein in human pulmonary cells

      Corresponding author: Shuye Zhang, shuye_zhang@fudan.edu.cn
      Corresponding author: Xiaoyan Zhang, zhangxiaoyan@fudan.edu.cn
      Corresponding author: Jianqing Xu, xujianqing@fudan.edu.cn
    • a. Clinical Center for Bio-Therapy, Zhongshan Hospital, Fudan University (Xiamen Branch), Shanghai, 200032, China;
    • b. Center for Infectious Disease Research, Science of Life Sciences, Westlake University, Hangzhou, 310024, China;
    • c. Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 201508, China

    Abstract: Influenza A virus (IAV), responsible for seasonal epidemics and recurring pandemics, represents a global threat to public health. Given the risk of a potential IAV pandemic, it is increasingly important to better understand virus-host interactions and develop new anti-viral strategies. Here, we reported nonmuscle myosin IIA (MYH9)-mediated regulation of IAV infection. MYH9 depletion caused a profound inhibition of IAV infection by reducing viral attachment and internalization in human lung epithelial cells. Surprisingly, overexpression of MYH9 also led to a significant reduction in viral productive infection. Interestingly, overexpression of MYH9 retained viral attachment, internalization, or uncoating, but suppressed the viral ribonucleoprotein (vRNP) activity in a minigenome system. Further analyses found that excess MYH9 might interrupt the formation of vRNP by interacting with the viral nucleoprotein (NP) and result in the reduction of the completed vRNP in the nucleus, thereby inhibiting subsequent viral RNA transcription and replication. Together, we discovered that MYH9 can interact with IAV NP protein and engage in the regulation of vRNP complexes, thereby involving viral replication. These findings enlighten new mechanistic insights into the complicated interface of host-IAV interactions, ultimately making it an attractive target for the generation of antiviral drugs.

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