Influenza A virus uses the aggresome processing machinery for host cell entry
Influenza A virus uses the aggresome processing machinery for host cell entry
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DOI：
10.1126/science.1257037
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发表时间：
2014-10-24
期刊：
影响因子：
56.9
通讯作者：
Yamauchi, Yohei
中科院分区：
文献类型：
--
作者：
Banerjee, Indranil;Miyake, Yasuyuki;Yamauchi, Yohei
在进入细胞期间，进入的甲型流感病毒（IAV）的衣壳必须在病毒核糖核蛋白（vRNP）可以进入细胞核进行复制之前未被涂覆。在晚期内吞空泡中血凝素介导的膜融合后，vRNP和基质蛋白彼此解离并分散在胞质溶胶内。在这里，我们发现对于衣壳解体，IAV利用宿主细胞的攻击性组形成和解体机制。衣壳通过携带未锚定的泛素链来模拟错误折叠的蛋白质聚集体，所述泛素链激活组蛋白去乙酰化酶6（HDAC6）依赖性途径。泛素结合结构域对于将HDAC6募集到病毒融合位点以及有效的脱壳和感染是必不可少的。攻击体加工机器的其他组件，包括动力蛋白，动力蛋白和肌球蛋白II也是必需的，这表明微管和肌动蛋白相关马达产生的物理力对IAV进入是必不可少的。
During cell entry, capsids of incoming influenza A viruses (IAVs) must be uncoated before viral ribonucleoproteins (vRNPs) can enter the nucleus for replication. After hemagglutinin-mediated membrane fusion in late endocytic vacuoles, the vRNPs and the matrix proteins dissociate from each other and disperse within the cytosol. Here, we found that for capsid disassembly, IAV takes advantage of the host cell's aggresome formation and disassembly machinery. The capsids mimicked misfolded protein aggregates by carrying unanchored ubiquitin chains that activated a histone deacetylase 6 (HDAC6)-dependent pathway. The ubiquitin-binding domain was essential for recruitment of HDAC6 to viral fusion sites and for efficient uncoating and infection. That other components of the aggresome processing machinery, including dynein, dynactin, and myosin II, were also required suggested that physical forces generated by microtubule-and actin-associated motors are essential for IAV entry.