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FBXO34 promotes latent HIV-1 activation by post-transcriptional modulation

Authors :
Xinyi Yang
Xiaying Zhao
Yuqi Zhu
Jingna Xun
Qin Wen
Hanyu Pan
Jinlong Yang
Jing Wang
Zhimin Liang
Xiaoting Shen
Yue Liang
Qinru Lin
Huitong Liang
Min Li
Jun Chen
Shibo Jiang
Jianqing Xu
Hongzhou Lu
Huanzhang Zhu
Source :
Emerging Microbes and Infections, Vol 11, Iss 1, Pp 2785-2799 (2022)
Publication Year :
2022
Publisher :
Taylor & Francis Group, 2022.

Abstract

Acquired immunodeficiency syndrome (AIDS) cannot be completely cured, mainly due to the existence of a latent HIV-1 reservoir. However, our current understanding of the molecular mechanisms underlying the establishment and maintenance of HIV-1 latent reservoir is not comprehensive. Here, using a genome-wide CRISPR-Cas9 activation library screening, we identified E3 ubiquitin ligase F-box protein 34 (FBXO34) and the substrate of FBXO34, heterogeneous nuclear ribonucleoprotein U (hnRNP U) was identified by affinity purification mass spectrometry, as new host factors related to HIV-1 latent maintenance. Overexpression of FBXO34 or knockout of hnRNP U can activate latent HIV-1 in multiple latent cell lines. FBXO34 mainly promotes hnRNP U ubiquitination, which leads to hnRNP U degradation and abolishment of the interaction between hnRNP U and HIV-1 mRNA. In a latently infected cell line, hnRNP U interacts with the ReV region of HIV-1 mRNA through amino acids 1-339 to hinder HIV-1 translation, thereby, promoting HIV-1 latency. Importantly, we confirmed the role of the FBXO34/hnRNP U axis in the primary CD4+ T lymphocyte model, and detected differences in hnRNP U expression levels in samples from patients treated with antiretroviral therapy (ART) and healthy people, which further suggests that the FBXO34/hnRNP U axis is a new pathway involved in HIV-1 latency. These results provide mechanistic insights into the critical role of ubiquitination and hnRNP U in HIV-1 latency. This novel FBXO34/hnRNP U axis in HIV transcription may be directly targeted to control HIV reservoirs in patients in the future.

Details

Language :
English
ISSN :
22221751
Volume :
11
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Emerging Microbes and Infections
Publication Type :
Academic Journal
Accession number :
edsdoj.5b603f802fa4313b266c253125b1ec6
Document Type :
article
Full Text :
https://doi.org/10.1080/22221751.2022.2140605