近日，中国医科大学Hong Shang及Guoxin Liang课题组探明了膜金属蛋白酶TRABD2A通过降解病毒Gag多蛋白来抑制静息CD4⁺T细胞中HIV-1子代的产生。 相关论文发表在2019年6月出版的《Nature Immunology》杂志上。

在这项研究中，团队发现细胞膜金属蛋白酶TRAB结构域包含蛋白2A(TRABD2A），通过降解质膜上的病毒结构前体多蛋白gag来抑制静息CD4⁺T细胞的子代病毒产生。消耗或抑制TRABD2A金属蛋白酶活性的可显著提高静息CD4⁺T细胞中HIV-1的产生。静息状态下的CD4⁺T细胞中TRABD2A的表达比激活状态下的CD4⁺T细胞高得多，T细胞激活后TRABD2A的表达显著降低。此外，再表达TRABD2A可增强活化的CD4⁺T细胞抵抗产生HIV1子代的能力。综上，这些结果阐明了静息CD4⁺T细胞抑制HIV-1子代的组装和产生的分子机制。

据悉，静息CD4⁺T细胞对人类免疫缺陷病毒1型（HIV1）的产生具有高度的抵抗力。然而，这种静息CD4⁺T细胞在感染病毒复制后期抑制病毒产生的机制仍不清楚。

附：英文原文

Title: Membrane metalloprotease TRABD2A restricts HIV-1 progeny production in resting CD4 + T cells by degrading viral Gag polyprotein

Author: Guoxin Liang, Li Zhao, Ying Qiao, Wenqing Geng, Xiaowei Zhang, Mei Liu, Jinxiu Dong, Haibo Ding, Hong Sun, Hong Shang

Issue&Volume: Volume 20 Issue 6, June 2019

Abstract: Resting CD4+ T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4+ T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease TRAB domain-containing protein 2A (TRABD2A) inhibited this production in resting CD4+ T cells by degrading the virion structural precursor polyprotein Gag at the plasma membrane. Depletion or inhibition of metalloprotease activity by TRABD2A profoundly enhanced HIV-1 production in resting CD4+ T cells. TRABD2A expression was much higher in resting CD4+ T cells than in activated CD4+ T cells and was considerably reduced by T cell activation. Moreover, reexpressing TRABD2A reinforced the resistance of activated CD4+ T cells to the production of HIV-1 progeny. Collectively, these results elucidate the molecular mechanism employed by resting CD4+ T cells to potently restrict the assembly and production of HIV-1 progeny.

DOI: 10.1038/s41590-019-0385-2

Source:https://www.nature.com/articles/s41590-019-0385-2