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Nef通过与病毒组装复合体结合来增强HIV-1的感染性。

Nef enhances HIV-1 infectivity via association with the virus assembly complex.

作者信息

Qi Mingli, Aiken Christopher

机构信息

Department of Microbiology and Immunology, Vanderbilt University School of Medicine, A-5301 Medical Center North, Nashville, TN 37232-2363, USA.

出版信息

Virology. 2008 Apr 10;373(2):287-97. doi: 10.1016/j.virol.2007.12.001. Epub 2008 Jan 14.

Abstract

The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle.

摘要

HIV-1辅助蛋白Nef通过促进感染进入后的早期步骤来增强病毒感染性。Nef在病毒产生细胞中发挥作用,对HIV-1颗粒进行有益修饰。Nef本身被整合到HIV-1颗粒中,并在病毒体成熟过程中被病毒蛋白酶切割。为了探究病毒体相关Nef在HIV-1感染中的作用,我们构建了一种融合蛋白,该蛋白由与Nef氨基末端相连的宿主蛋白亲环素A(CypA)组成。所得的CypA-Nef蛋白增强了Nef缺陷型HIV-1颗粒的感染性,并在颗粒组装过程中通过与Gag结合而特异性地整合到病毒体中。对CypA-Nef与Gag结合的药理或基因抑制可阻止CypA-Nef整合到病毒体中,并抑制感染性增强。我们的结果表明,Nef增强感染性需要其与组装中的HIV-1颗粒的一个组分相结合。

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本文引用的文献

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Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef.发动蛋白2是Nef增强HIV-1感染性所必需的。
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6812-7. doi: 10.1073/pnas.0607622104. Epub 2007 Apr 5.

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