HIV-1 N-myristoylation-dependent hijacking of late endosomes/lysosomes to drive Gag assembly in macrophages.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2024-11-15 Epub Date: 2024-11-21 DOI:10.1242/jcs.263588
Gabriel I Guajardo-Contreras, Ana L Abdalla, Alex Chen, Meijuan Niu, Erwan Beauchamp, Luc G Berthiaume, Alan W Cochrane, Andrew J Mouland
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Abstract

Macrophages represent an important viral reservoir in HIV-1-infected individuals. Different from T cells, HIV-1 assembly in macrophages occurs at intracellular compartments termed virus-containing compartments (VCCs). Our previous research in HeLa cells - in which assembly resembles that found in infected T cells - suggested that late endosomes/lysosomes (LELs) play a role in HIV-1 trafficking towards its assembly sites. However, the role of LELs during assembly at VCCs is not fully understood. Herein, we used the HIV-1-inducible cell line THP-1 GagZip as a model to study HIV-1 Gag intracellular trafficking and assembly in macrophages. We demonstrated LEL involvement at VCCs using various microscopy techniques and biochemical approaches. Live-cell imaging revealed that HIV-1 repositions LELs towards the plasma membrane and modulates their motility. We showed that Arl8b-mediated LEL repositioning is not responsible for Gag trafficking to VCCs. Additionally, the inhibition of myristoylation by PCLX-001 decreased the presence of Gag on endosomes and inhibited VCC formation in both the THP-1 cell line and primary macrophages. In conclusion, we present evidence supporting the idea that HIV-1 manipulates the LEL trajectory to guide Gag to VCCs in an N-myristoylation-dependent manner.

HIV-1 N-肉豆蔻酰化依赖性劫持晚期内体/溶酶体,以驱动巨噬细胞中 Gag 的组装。
巨噬细胞是 HIV-1 感染者体内重要的病毒库。与 T 细胞不同,HIV-1 在巨噬细胞中的组装发生在细胞内称为含病毒区室(VCC)的区室中。我们之前在 HeLa 细胞中进行的研究表明,晚期内体/溶酶体(LEL)在 HIV-1 向其装配位点的运输过程中发挥了作用。然而,LEL 在 VCC 组装过程中的作用还不完全清楚。在本文中,我们以HIV-1诱导细胞系THP-1 GagZip为模型,研究了HIV-1 Gag在巨噬细胞中的胞内转运和组装。我们利用各种显微镜技术和生化方法证明了 LEL 在 VCC 中的参与。活细胞成像显示,HIV-1 将 LEL 向质膜重新定位并调节其运动。我们发现,Arl8b 介导的 LEL 重定位并不负责 Gag 向 VCCs 的贩运。此外,在细胞系和原代巨噬细胞中,通过 PCLX-001 抑制肉豆蔻酰化可减少 Gag 在内质体上的存在并抑制 VCC 的形成。总之,我们提出的证据支持了这样一种观点,即 HIV-1 操纵 LEL 轨迹,以 N-肉豆蔻酰化依赖的方式将 Gag 引导至 VCC。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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