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 understan...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 virushost 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.展开更多
基质蛋白1(matrix protein 1,M1)提供了甲型流感病毒蛋白之间一个相互作用的“平台”。M1不仅维持了病毒粒子的形态和表面蛋白的稳定,而且还将8个分节段的基因组固定在病毒的核心位置,最终协调病毒的高效组装和出芽。由于M1的高度保守性...基质蛋白1(matrix protein 1,M1)提供了甲型流感病毒蛋白之间一个相互作用的“平台”。M1不仅维持了病毒粒子的形态和表面蛋白的稳定,而且还将8个分节段的基因组固定在病毒的核心位置,最终协调病毒的高效组装和出芽。由于M1的高度保守性,研究人员对其关注度相对较低。为此,对M1的结构和功能进行了详实的回顾,并展望了M1作为新型抗病毒药物靶点的潜能。通过对甲型流感病毒M1的深入理解,以期提高我们对其他病毒基质蛋白的关注度和研究兴趣。展开更多
基金supported by the National Natural Science Foundation of China(82071788,81901598,81771704,and 82041015)National Key R&D Program of China(2022YFC2604100).
文摘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 virushost 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.
文摘基质蛋白1(matrix protein 1,M1)提供了甲型流感病毒蛋白之间一个相互作用的“平台”。M1不仅维持了病毒粒子的形态和表面蛋白的稳定,而且还将8个分节段的基因组固定在病毒的核心位置,最终协调病毒的高效组装和出芽。由于M1的高度保守性,研究人员对其关注度相对较低。为此,对M1的结构和功能进行了详实的回顾,并展望了M1作为新型抗病毒药物靶点的潜能。通过对甲型流感病毒M1的深入理解,以期提高我们对其他病毒基质蛋白的关注度和研究兴趣。
