首页|Nonmuscle myosin ⅡA promotes the internalization of influenza A virus and regulates viral polymerase activity through interacting with nucleoprotein in human pulmonary cells
Nonmuscle myosin ⅡA promotes the internalization of influenza A virus and regulates viral polymerase activity through interacting with nucleoprotein in human pulmonary cells
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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 mini-genome 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.
Myosin ⅡA(MYH9)Influenza A virus(IAV)vRNP activityVirus-host interactionsVirus entry
Clinical Center for Bio-Therapy,Zhongshan Hospital,Fudan University(Xiamen Branch),Shanghai,200032,China
Center for Infectious Disease Research,Science of Life Sciences,Westlake University,Hangzhou,310024,China
Shanghai Public Health Clinical Center&Institutes of Biomedical Sciences,Shanghai Medical College,Fudan University,Shanghai,201508,China
National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key R&D Program of China