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PARP1 Might Substitute HSF1 to Reactivate Latent HIV-1 by Binding to Heat Shock Element

Authors :
Xinfeng Xu
Yingtong Lin
Xiaoyun Zeng
Chan Yang
Siqin Duan
Liqiong Ding
Wanzhen Lu
Jian Lin
Xiaoyan Pan
Xiancai Ma
Shuwen Liu
Source :
Cells, Vol 11, Iss 15, p 2331 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

At present, the barrier to HIV-1 functional cure is the persistence of HIV-1 reservoirs. The “shock (reversing latency) and kill (antiretroviral therapy)” strategy sheds light on reducing or eliminating the latent reservoir of HIV-1. However, the current limits of latency-reversing agents (LRAs) are their toxicity or side effects, which limit their practicability pharmacologically and immunologically. Our previous research found that HSF1 is a key transcriptional regulatory factor in the reversion of HIV-1 latency. We then constructed the in vitro HSF1-knockout (HSF1-KO) HIV-1 latency models and found that HSF1 depletion inhibited the reactivation ability of LRAs including salubrinal, carfizomib, bortezomib, PR-957 and resveratrol, respectively. Furthermore, bortezomib/carfizomib treatment induced the increase of heat shock elements (HSEs) activity after HSF1-KO, suggesting that HSEs participated in reversing the latent HIV-1. Subsequent investigation showed that latent HIV-1-reversal by H2O2-induced DNA damage was inhibited by PARP1 inhibitors, while PARP1 was unable to down-regulate HSF1-depleted HSE activity, indicating that PARP1 could serve as a replaceable protein for HSF1 in HIV-1 latent cells. In summary, we succeeded in finding the mechanisms by which HSF1 reactivates the latent HIV-1, which also provides a theoretical basis for the further development of LRAs that specifically target HSF1.

Details

Language :
English
ISSN :
20734409
Volume :
11
Issue :
15
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.25274a6ce9b9451883f6472a506338cd
Document Type :
article
Full Text :
https://doi.org/10.3390/cells11152331