TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR

作者全名："Ran, Xiang-Hong; Zhu, Jia-Wu; Ni, Run-Ze; Zheng, Yong-Tang; Chen, Ya-Yun; Zheng, Wei-Hua; Mu, Dan"

作者地址："[Ran, Xiang-Hong; Ni, Run-Ze; Chen, Ya-Yun; Zheng, Wei-Hua; Mu, Dan] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Zhu, Jia-Wu] Kunming Med Univ, Sch Basic Med Sci, Kunming, Yunnan, Peoples R China; [Zheng, Yong-Tang] Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China"

通信作者："Mu, D (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China."

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:001047512000023

JCR分区：Q1

影响因子：14.7

年份：2023

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Tripartite motif-containing protein 5 alpha (TRIM5 alpha) is generally known to block the postentry events of HIV-1. Here, we report an uncharacterized role for TRIM5 alpha in the maintenance of viral latency. Knockdown of TRIM5 alpha potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5 alpha. TRIM5 alpha suppresses TNF alpha-activated HIV-1 LTR-driven as well as NF-kappa B- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Mechanistically, TRIM5 alpha binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-kappa B p50 and Sp1. ChIPqPCR analyses further reveal that the association of TRIM5 alpha with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Conserved suppression effects of TRIM5 alpha orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. These findings provide new insights into the molecular mechanisms by which proviral latency is initially established and activatable proviruses are resilenced by histone deacetylase recruitment."

基金机构：Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN202000424]; Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0253]; National Natural Science Foundation of China [82160388]; program Innovative Research Team in Science and Technology in Kunming Medical University [CXTD202202]; Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation [201901D070045]

基金资助正文："We thank Dr. Ping Lu (University of Massachusetts Medical School) for critical reading and constructive suggestions of this manuscript. This work was supported by grants from the Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJQN202000424), Chongqing Natural Science Foundation (cstc2021jcyj-msxmX0253), Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation (201901D070045), the National Natural Science Foundation of China (82160388), and the program Innovative Research Team in Science and Technology in Kunming Medical University (CXTD202202)."