HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus.

HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus.
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DOI:
10.1038/ncomms7660
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发表时间:
2015-03-30
影响因子:
16.6
通讯作者:
Naghavi, Mojgan H.
Naghavi, Mojgan H.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Malikov, Viacheslav;da Silva, Eveline Santos;Jovasevic, Vladimir;Bennett, Geoffrey;Vieira, Daniel A. de Souza Aranha;Schulte, Bianca;Diaz-Griffero, Felipe;Walsh, Derek;Naghavi, Mojgan H.

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包括许多病毒在内的物质在细胞内的运输涉及由运动蛋白介导的微管上的定向运动。虽然许多病毒结合了方向性相反的马达,但它们是如何与这些马达结合并控制这些马达来完成定向运动的,人们仍然知之甚少。在这里,我们发现人类免疫缺陷病毒1型(HIV-1)与运动蛋白1接头蛋白、束状和伸长因子zeta 1 (FEZ1)相关。rnai介导的FEZ1耗尽阻断了早期感染,病毒颗粒表现出双向运动,但没有向细胞核的净运动。此外,动力蛋白和动力蛋白-1发动机都是HIV-1运输到细胞核所必需的。最后,外源性表达的FEZ1促进早期HIV-1感染的能力需要与激酶-1结合。我们的研究结果表明,相反的马达既有助于HIV-1的早期运动,也确定了激酶-1适配器FEZ1作为衣壳相关的宿主调节剂,这一过程被HIV-1篡位,以完成向细胞核的净向内运动。
Intracellular transport of cargos, including many viruses, involves directed movement on microtubules mediated by motor proteins. While a number of viruses bind motors of opposing directionality, how they associate with and control these motors to accomplish directed movement remains poorly understood. Here we show that human immunodeficiency virus type 1 (HIV-1) associates with the kinesin-1 adaptor protein, Fasiculation and Elongation Factor zeta 1 (FEZ1). RNAi-mediated FEZ1 depletion blocks early infection, with virus particles exhibiting bidirectional motility but no net movement to the nucleus. Furthermore, both dynein and kinesin-1 motors are required for HIV-1 trafficking to the nucleus. Finally, the ability of exogenously expressed FEZ1 to promote early HIV-1 infection requires binding to kinesin-1. Our findings demonstrate that opposing motors both contribute to early HIV-1 movement and identify the kinesin-1 adaptor, FEZ1 as a capsid-associated host regulator of this process usurped by HIV-1 to accomplish net inward movement toward the nucleus.
腺病毒通过细胞质动力蛋白与病毒capsid己糖亚基的直接相互作用进行转运。
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