HIV p17 enhances T cell proliferation by suppressing autophagy through the p17-OLA1-GSK3β axis under nutrient starvation
HIV p17 enhances T cell proliferation by suppressing autophagy through the p17-OLA1-GSK3β axis under nutrient starvation
复制标题
HIV p17 在营养饥饿下通过 p17-OLA1-GSK3 β 轴抑制自噬，从而增强 T 细胞增殖
DOI：
10.1002/jmv.26423
复制
发表时间：
2020-08-21
影响因子：
12.7
通讯作者：
Liu, Xinqi
中科院分区：
文献类型：
--
作者：
Lu, Jing;Jia, Jiayuan;Liu, Xinqi
营养饥饿是T细胞活化过程中常见的现象。病原体感染后，大量免疫细胞迁移到感染部位，抗原特异性T细胞被激活;随后通过克隆扩增快速增殖。细胞的急剧膨胀通常会导致营养不足。细胞自噬通常被上调作为维持身体能量需求的一种方式。在感染过程中，人类免疫缺陷病毒（HIV）会选择一系列宿主细胞代谢途径进行复制。据报道，Env、Nef和Vpr等几种HIV蛋白质参与了自噬相关过程。在这份报告中，我们确定了HIV p17蛋白作为抑制T细胞自噬过程的主要因素，特别是在葡萄糖饥饿条件下。HIV p17与Obg样ATP酶1（OLA 1）相互作用，破坏OLA 1-糖原合成酶激酶-3 β（GSK 3 β）复合物，导致GSK 3 β过度活化。因此，HIV感染的T细胞在葡萄糖饥饿下会发生优先增殖。自噬的抑制也通过拮抗自噬的抗病毒作用来帮助HIV复制。我们的研究显示了一种新的细胞途径，HIV可以通过HIV负载的T细胞的先前增殖劫持病毒传播，并可能为获得性免疫缺陷综合征干预提供新的治疗靶点。
Nutrient starvation is a common phenomenon that occurs during T cell activation. Upon pathogen infection, large amounts of immune cells migrate to infection sites, and antigen-specific T cells are activated; this is followed by rapid proliferation through clonal expansion. The dramatic expansion of cells will commonly lead to nutrient shortage. Cellular autophagy is often upregulated as a way to sustain the body's energy requirements. During infection, human immunodeficiency virus (HIV) co-opts a series of host cell metabolic pathways for replication. Several HIV proteins, such as Env, Nef, and Vpr, have already been reported as being involved in autophagy-related processes. In this report, we identified that the HIV p17 protein acts as a major factor in suppressing the autophagic process in T cells, especially under glucose starvation condition. HIV p17 interacts with Obg-like ATPase 1 (OLA1) and disrupts OLA1-glycogen synthase kinase-3 beta (GSK3 beta) complex, leading to GSK3 beta hyperactivation. Consequently, a prior proliferation of HIV-infected T cells under glucose starvation will occur. The inhibition of autophagy also aids HIV replication by antagonizing the antiviral effect of autophagy. Our study shows a new cellular pathway that HIV can hijack for viral spreading by a prior proliferation of HIV-loaded T cells and may provide new therapeutic targets for acquired immunodeficiency syndrome intervention.