Fusion and Uncoating of the Influenza Virion

Uncoating of viral particles takes place in the host cell endosome. Acidification of the endosome promotes fusion of the viral and endosomal membranes, causing a structural change in the viral hemagglutinin (HA) and freeing the fusion peptide of its HA2 subunit to interact with the endosome membrane. The concerted structural change of several HA molecules opens up a pore through which the viral RNP passes into the cytosol of the cell. The precise timing and the location of uncoating (early vs. late endosomes) depends on the pH-mediated transition of the specific HA molecule involved. The virus-associated M2 ion channel protein allows the influx of H+ ions into the virion, which disrupts protein-protein interactions, resulting in the release of RNP free of the viral M1 matrix protein. Thus the HA mediated fusion of the viral membrane with the endosomal membrane and the M2-mediated release of the RNP results in the release of the RNP complex into the cytosol. Amantadine and rimantadine have been shown to block the ion channel activity of the M2 protein and thus interfere with uncoating.

病毒颗粒的脱壳过程发生在宿主细胞的内体中。内体的酸化促进了病毒膜与内体膜的融合，导致病毒血凝素（HA）结构发生改变，并使HA2亚单位的融合肽得以与内体膜相互作用。多个HA分子的协同结构变化打开了一个通道，病毒核糖核蛋白（RNP）通过该通道进入细胞的细胞质中。脱壳的精确时间和位置（早期或晚期内体）取决于特定HA分子参与的pH介导的过渡。与病毒相关的M2离子通道蛋白允许H+离子流入病毒颗粒，从而破坏蛋白质-蛋白质相互作用，导致RNP与病毒M1基质蛋白的释放。因此，HA介导的病毒膜与内体膜的融合以及M2介导的RNP释放导致RNP复合物进入细胞质。阿曼达林和利马塔丁已被证明可以阻断M2蛋白的离子通道活性，从而干扰脱壳过程。