Madsen Jesper J, Rossman Jeremy S
Global and Planetary Health, Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, Tampa, FL, USA.
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Subcell Biochem. 2023;106:441-459. doi: 10.1007/978-3-031-40086-5_16.
The cholesterol of the host cell plasma membrane and viral M2 protein plays a crucial role in multiple stages of infection and replication of the influenza A virus. Cholesterol is required for the formation of heterogeneous membrane microdomains (or rafts) in the budozone of the host cell that serves as assembly sites for the viral components. The raft microstructures act as scaffolds for several proteins. Cholesterol may further contribute to the mechanical forces necessary for membrane scission in the last stage of budding and help to maintain the stability of the virus envelope. The M2 protein has been shown to cause membrane scission in model systems by promoting the formation of curved lipid bilayer structures that, in turn, can lead to membrane vesicles budding off or scission intermediates. Membrane remodeling by M2 is intimately linked with cholesterol as it affects local lipid composition, fluidity, and stability of the membrane. Thus, both cholesterol and M2 protein contribute to the efficient and proper release of newly formed influenza viruses from the virus-infected cells.
宿主细胞质膜中的胆固醇和病毒M2蛋白在甲型流感病毒感染和复制的多个阶段发挥着关键作用。胆固醇是在宿主细胞芽生区形成异质性膜微结构域（或脂筏）所必需的，这些微结构域充当病毒成分的组装位点。脂筏微结构充当多种蛋白质的支架。胆固醇可能进一步有助于芽生最后阶段膜分裂所需的机械力，并有助于维持病毒包膜的稳定性。M2蛋白已被证明在模型系统中通过促进弯曲脂质双层结构的形成导致膜分裂，而弯曲脂质双层结构反过来又可导致膜囊泡出芽或分裂中间体。M2介导的膜重塑与胆固醇密切相关，因为它影响膜的局部脂质组成、流动性和稳定性。因此，胆固醇和M2蛋白都有助于新形成的流感病毒从病毒感染细胞中有效且适当地释放。
