Hepatitis C virus: viral proteins on the move
Hepatitis C virus: viral proteins on the move
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DOI：
10.1042/bst0370986
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发表时间：
2009-10-01
影响因子：
3.9
通讯作者：
McLauchlan, John
中科院分区：
文献类型：
--
作者：
McLauchlan, John
现在越来越多的证据表明，LD（脂滴）在传染性 HCV（丙型肝炎病毒）的产生中发挥着核心作用，并参与病毒组装。在受感染细胞的 LID 表面检测到两种病毒蛋白，即形成衣壳的核心蛋白和参与病毒 RNA 合成的复合物成分 NS5A（非结构性 SA 蛋白）。这两种蛋白质之间的相互作用可能对于将 RNA 复制位点锚定到液滴上以启动病毒组装至关重要。特别是针对核心的要求受到了相当多的关注，因为其与 LD 相互作用的性质可能在确定病毒颗粒生产效率方面发挥关键作用。除了附着在液滴上之外，核心还能够改变它们在细胞内的分布，并将它们引导至微管组织中心。破坏微管的抑制剂会阻止这种核心的重新分配，从而导致病毒产量减少。因此，LDs 动力学的改变可能有助于 HCV 的组装和释放。 HCV 靶向 LIDS 的目的可能与它们对肝细胞中 VLDL（极低密度脂蛋白）形成的贡献有关，因为感染患者中循环的病毒与脂蛋白相关。因此，HCV 可以利用 LD 在脂蛋白颗粒形成中发挥的作用作为其生命周期的一部分，并通过病毒成分与这些细胞内储存细胞器的直接相互作用来进入该途径。
There is now increasing evidence that LDs (lipid droplets) play a central role in the production of infectious HCV (hepatitis C virus) and participate in virus assembly. Two viral proteins, namely core, which forms the capsid, and NS5A (non-structural SA protein), a component of complexes engaged in viral RNA synthesis, are detected at LID surfaces in infected cells. interactions between the two proteins may be critical for anchoring RNA replication sites to droplets for initiating virus assembly. The requirements for targeting of core in particular has received considerable attention since the nature of its interaction with LDs could play a key role in determining the efficiency of virion production. As well as attaching to droplets, core is able to alter their intracellular distribution and direct them towards the microtubule organizing centre. inhibitors that disrupt microtubules block this redistribution by core and there is a concomitant decrease in virus production. Therefore altered dynamics of LDs may contribute to HCV assembly and release. The purpose of targeting LIDS by HCV may be linked to their contribution to the formation of VLDLs (very-low-density lipoproteins) in hepatocytes since virus circulating in infected patients is associated with lipoprotein. Thus HCV may utilize the role played by LDs in the formation of lipoprotein particles as part of its life cycle and access this pathway by direct interaction of viral components with these intracellular storage organelles.