An important cellular mechanism regulating HIV latency and discovering a high-efficiency HIV latency activator

On January 5th, the research group of Wang Jianhua and Chen Ling of Guangzhou Health Institute cooperated to reveal the important cell signaling pathways that regulate HIV latency, and discovered a small molecule compound that can efficiently activate latent HIV, and suggested that the compound could be used for the cure of HIV latency.
Pharmacological suppression of glycogen synthase kinase-3 reactivates HIV-1 from latency via activating Wnt / β-catenin / TCF1 axis in CD4 + T cells was published in an international academic journal Emerging Microbes & Infections on
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As a retrovirus, HIV can integrate into the host genome after reverse transcription of its genome into DNA to establish latent infection
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CD4+ T cells are the main latent cells of HIV; in histological anatomy, mesenteric lymph nodes, intestinal mucosal tissue, reproductive tract mucosal tissue and the central nervous system are the main "hidden" sites of HIV

The development of HIV/AIDS eradication strategies requires an in-depth analysis of the HIV latency mechanism
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Wang Jianhua's team has systematically studied the HIV latency regulation mechanism in the early stage, and found a variety of key host targets for regulating HIV latency

In this study, it was found that the small molecule compound 6-BIO can efficiently activate latent HIV in CD4+ T cells, and the effect of 6-BIO on activating latent virus was evaluated using a rhesus monkey model infected with SIV (simian immunodeficiency virus)
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The paper suggests that 6-BIO can be used as a highly effective LRA combined with ART or cellular immunotherapy, suitable for an "activation-kill" strategy for HIV latent eradication

In this paper, the mechanism of 6-BIO activation of latent HIV in CD4+ T cells was studied
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Researchers found that 6-BIO activates the intracellular Wnt/β-catenin/TCF1 signaling pathway by inhibiting intracellular GSK-3 (glycogen synthase kinase-3); activation of this pathway leads to the recruitment of the transcription factor TCF1 to the HIV promoter LTR region, and altered LTR region histone epigenetic modifications, thereby driving HIV proviral DNA transcription and activation of latent virus

The corresponding authors of the paper are Wang Jianhua and Chen Ling;The first authors are: Wen Jing (Shanghai Pasteur Institute), Li Xin (Guangzhou Health Center) and Zhao Qingxia (Zhengzhou Sixth People's Hospital)
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The research was supported by Chang Junbiao's team at Henan Normal University, Deng Kai's team at Sun Yat-Sen University, and Su Xiao and Wang Haikun's team at the Pasteur Institute in Shanghai

Paper link

Paper summary figure : 6-BIO activates latent HIV in CD4 ⁺ T cells
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Using latent HIV-infected CD4 ^{+ T cell lines, HIV-latent CD4 +} T cells isolated from HIV-infected patients, and SIV-infected rhesus monkey models, it was demonstrated that the small molecule compound 6-BIO can efficiently activate latent HIV
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Molecularly, 6-BIO activates the Wnt/β-catenin/TCF1 signaling pathway by inhibiting glycogen synthase kinase-3 (GSK3) in CD4 ⁺ T cells, promotes the recruitment of TCF1 to the HIV promoter LTR region, and changes the LTR region group.