甲型流感病毒蛋白和遗传物质在宿主细胞质内顺向转运过程及其机制

Mechanism underlying the anterograde transport of the influenza A virus transmembrane proteins and genome in host cytoplasm

摘要:

流感病毒的蛋白和基因组在宿主细胞内能否正确地转运到相关部位，直接影响到病毒颗粒的形态发生。流感病毒跨膜蛋白 (HA、NA和M2) 主要通过宿主细胞的运输膜泡实现转运，而宿主细胞的蛋白转运机器参与了这一过程。新合成的流感病毒核糖核蛋白复合物 (vRNPs) 出核后，通过与活化的Rab11相结合，聚集于邻近微管组织中心 (MTOC) 的胞内体。然后以运输小膜泡的形式，沿着MTOC的微管网络向细胞膜方向转运。跨膜蛋白和基因组在细胞质内的转运受一些宿主因子的调控，如ARHGAP21和小G蛋白Cdc42能够调节NA蛋白向细胞膜转运，Rab11协助vRNPs从MTOC向细胞膜转运。文中主要讨论新合成的流感病毒跨膜蛋白和遗传物质在宿主细胞质内的顺向转运 (Anterograde transport) 过程与调控。

Abstract:

Influenza virus assembly requires the completion of viral protein and vRNP transport to the assembly site at the plasma membrane. Therefore, efficient regulation of intracellular transport of the viral proteins and vRNPs to the surface of the host cell is especially important for virus morphogenesis. Influenza A virus uses the machineries of host cells to transport its own components including ribonucleoproteins (vRNPs) and three transmembrane proteins hemagglutinin (HA), neuraminidase (NA) and matrix 2 protein (M2). It has been shown that newly synthesized vRNPs are associated with active form of Rab11 and accumulate at recycling endosomes adjacent to the microtubule organizing center (MTOC) following nuclear export. Subsequently, they are transported along the microtubule network toward the plasma membranes in cargo vesicles. The viral transmembrane proteins are translated on the rough endoplasmic reticulum and transported to the virus assembly site at the plasma membrane. It has been found that several host factors such as ARHGAP21 and GTPase Cdc42 are involved in regulation of intracellular trafficking of influenza A virus transmembrane proteins including NA. In this review, we will highlight the current knowledge about anterograde transport and its regulation of the influenza A virus transmembrane proteins and genome in the host cytoplasm.