Spinoculation Triggers Dynamic Actin and Cofilin Activity That Facilitates HIV-1 Infection of Transformed and Resting CD4 T Cells
Spinoculation Triggers Dynamic Actin and Cofilin Activity That Facilitates HIV-1 Infection of Transformed and Resting CD4 T Cells
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DOI：
10.1128/jvi.05170-11
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Wu, Yuntao
中科院分区：
文献类型：
--
作者：
Guo, Jia;Wang, Weifeng;Wu, Yuntao
离心接种，或spinoculation，被广泛用于病毒学研究，以提高病毒感染。然而，这一机制仍不清楚。使用HIV-1感染的人T细胞作为一个模型，我们表明，spinoculation触发动态肌动蛋白和cofilin的活动，可能是由于细胞对离心应力的反应。这种肌动蛋白活性还导致HIV-1受体和辅助受体CD 4和CXCR 4的上调，增强病毒结合和进入。我们还表明，肌动蛋白抑制剂，jasplakinastatin，减少自旋介导的增强。此外，小干扰RNA（siRNA）敲低LIMK 1，一种cofilin激酶，降低增强。这些结果表明，自旋介导的增强不能简单地解释由病毒集中效应，而是，它是再加上自旋诱导的细胞骨架动力学，促进受体动员，病毒进入，和postentry过程。我们的研究结果强调了cofilin和动态细胞骨架对病毒感染启动的重要性。我们的研究结果还表明，在数据解释时，细胞是spinoculated需要谨慎;一些自旋诱导的细胞的宽容可能超出了感染病毒的自然能力。
Centrifugal inoculation, or spinoculation, is widely used in virology research to enhance viral infection. However, the mechanism remained obscure. Using HIV-1 infection of human T cells as a model, we demonstrate that spinoculation triggers dynamic actin and cofilin activity, probably resulting from cellular responses to centrifugal stress. This actin activity also leads to the upregulation of the HIV-1 receptor and coreceptor, CD4 and CXCR4, enhancing viral binding and entry. We also demonstrate that an actin inhibitor, jasplakinolide, diminishes spin-mediated enhancement. In addition, small interfering RNA (siRNA) knockdown of LIMK1, a cofilin kinase, decreases the enhancement. These results suggest that spin-mediated enhancement cannot be explained simply by a virus-concentrating effect; rather, it is coupled with spin-induced cytoskeletal dynamics that promote receptor mobilization, viral entry, and postentry processes. Our results highlight the importance of cofilin and a dynamic cytoskeleton for the initiation of viral infection. Our results also indicate that caution needs to be taken in data interpretation when cells are spinoculated; some of the spin-induced cellular permissiveness may be beyond the natural capacity of an infecting virus.