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

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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