Microtubule‐dependent retrograde transport of bovine immunodeficiency virus
Microtubule‐dependent retrograde transport of bovine immunodeficiency virus
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DOI：
10.1111/j.1462-5822.2010.01453.x
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发表时间：
2010-08
影响因子：
3.4
通讯作者：
Yang Su;W. Qiao;Tingting Guo;Juan Tan;Zhe Li;Yan Chen;Xin Li;Yue Li;Jun Zhou;Qi-min C
中科院分区：
文献类型：
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作者：
Yang Su;W. Qiao;Tingting Guo;Juan Tan;Zhe Li;Yan Chen;Xin Li;Yue Li;Jun Zhou;Qi-min C
微管是细胞骨架的重要组成部分，参与细胞分裂和迁移等多种细胞过程。此外，越来越多的证据表明，微管在细胞内病毒运输中发挥了作用。在这项研究中，我们发现药物破坏微管显著阻止了牛免疫缺陷病毒(BIV)从细胞外围到核周区域的移动，这一过程被称为逆行运输。微管相关运动蛋白Dynein的抑制功能也观察到了类似的效果。通过酵母双杂交实验，我们发现BIV的衣壳蛋白(CA)与动力蛋白轻链成分LC8相互作用。免疫沉淀和GST-Pull-Down实验进一步证实了CA和LC_8在哺乳动物细胞中的相互作用。此外，我们的数据显示，Lc8是BIV颗粒和微管之间的连接物。Lc8基因表达下调可显著抑制BIV的逆行转运。我们的发现提供了第一个证据，表明传入的BIV粒子利用宿主微管/动力蛋白机制向核周区域运输。此外，我们的数据表明，LC8-CA相互作用是设计抗病毒策略的潜在靶点。
Microtubules are essential components of the cytoskeleton that participate in a variety of cellular processes such as cell division and migration. In addition, there is a growing body of evidence implicating a role for microtubules in intracellular viral transport. In this study, we found that pharmacological disruption of microtubules remarkably blocked bovine immunodeficiency virus (BIV) movement from the cell periphery to the perinuclear region, a process known as retrograde transport. A similar effect was observed by inhibiting function of the microtubule‐associated motor protein dynein. By yeast two‐hybrid assay, we found that the capsid protein (CA) of BIV interacted with the dynein light‐chain component LC8. Immunoprecipitation and GST‐pulldown assays further demonstrated an interaction between CA and LC8 in mammalian cells. In addition, our data revealed LC8 as a linker between BIV particles and microtubules. Retrograde transport of BIV was significantly inhibited by knockdown of LC8 expression. Our findings present the first evidence that incoming BIV particles employ host microtubule/dynein machinery for transport towards the perinuclear region. In addition, our data indicate that the LC8–CA interaction is a potential target for the design of antiviral strategies.