Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8
Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8
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DOI：
10.1242/jcs.00613
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发表时间：
2003-08-15
影响因子：
4
通讯作者：
Saïb, A
中科院分区：
文献类型：
--
作者：
Petit, C;Giron, ML;Saïb, A
最近的研究部分揭开了细胞蛋白在逆转录病毒复制中的作用，特别是在病毒组装期间。矛盾的是，人们对逆转录病毒在感染早期到达细胞核的途径知之甚少。为了深入了解病毒复制的这一阶段，我们研究了泡沫逆转录病毒的运输，并先前表明，传入的病毒蛋白在病毒基因组核易位之前到达微管组织中心(MTOC)。在这里，我们显示了传入的病毒以自由和结构化衣壳的形式集中在MTOC周围。有趣的是，Gag蛋白是病毒衣壳的支架成分，在没有任何其他病毒成分的情况下，它以微管和动力蛋白/动力蛋白依赖的方式靶向转基因细胞的胞体周围区域。GAG向中心体的运输需要在分子的N-末端至少有30个氨基酸的螺旋卷曲基序。最后，我们描述了Gag和动力蛋白轻链8之间的直接相互作用，这可能解释了在病毒基因组核导入之前，传入衣壳到中心体的特定路线。
The role of cellular proteins in the replication of retroviruses, especially during virus assembly, has been partly unraveled by recent studies. Paradoxically, little is known about the route taken by retroviruses to reach the nucleus at the early stages of infection. To get insight into this stage of virus replication, we have studied the trafficking of foamy retroviruses and have previously shown that incoming viral proteins reach the microtubule organizing center (MTOC) prior to nuclear translocation of the viral genome. Here, we show that incoming viruses concentrate around the MTOC as free and structured capsids. Interestingly, the Gag protein, the scaffold component of viral capsids, targets the pericentrosomal region in transfected cells in the absence of any other viral components but in a microtubule- and dynein/dynactin-dependent manner. Trafficking of Gag towards the centrosome requires a minimal 30 amino acid coiled-coil motif in the N-terminus of the molecule. Finally, we describe a direct interaction between Gag and dynein light chain 8 that probably accounts for the specific routing of the incoming capsids to the centrosome prior to nuclear import of the viral genome.