Resveratrol Promotes HIV-1 Tat Accumulation via AKT/FOXO1 Signaling Axis and Potentiates Vorinostat to Antagonize HIV-1 Latency

Author(s): Zeming Feng, Zhengrong Yang, Xiang Gao, Yuhua Xue, Xiaohui Wang*

Journal Name: Current HIV Research

Volume 19 , Issue 3 , 2021


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Abstract:

Background: The latent reservoir of HIV-1 is a major barrier to achieving the eradication of HIV-1/AIDS. One strategy is termed “shock and kill”, which aims to awaken the latent HIV-1 using latency reversing agents (LRAs) to replicate and produce HIV-1 particles. Subsequently, the host cells containing HIV-1 can be recognized and eliminated by the immune response and anti-retroviral therapy. Although many LRAs have been found and tested, their clinical trials were dissatisfactory.

Objective: To aim of the study was to investigate how resveratrol reactivates silent HIV-1 transcription and assess if resveratrol could be a candidate drug for the “shock” phase in “shock and kill” strategy.

Methods: We used established HIV-1 transcription cell models (HeLa-based NH1 and NH2 cells) and HIV-1 latent cell models (J-Lat A72 and Jurkat 2D10 cells). We performed resveratrol treatment on these cell lines and studied the mechanism of how resveratrol stimulates HIV-1 gene transcription. We also tested resveratrol’s bioactivity on primary cells isolated from HIV-1 latent infected patients.

Results: Resveratrol promoted HIV-1 Tat protein levels, and resveratrol-induced Tat promotion was found to be dependent on the AKT/FOXO1 signaling axis. Resveratrol could partially dissociate P-TEFb (Positive Transcription Elongation Factor b) from 7SK snRNP (7SK small nuclear Ribonucleoprotein) and promote Tat-SEC (Super Elongation Complex) interaction. Preclinical studies showed that resveratrol potentiated Vorinostat to awaken HIV-1 latency in HIV-1 latent infected cells isolated from patients.

Conclusion: We found a new mechanism of resveratrol stimulating the production of HIV-1. Resveratrol could be a promising candidate drug to eradicate HIV-1 reservoirs.

Keywords: HIV-1, Reservoirs, Resveratrol, HIV-1 Tat, AKT/FOXO1, P-TEFb, Super Elongation Complex.

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Article Details

VOLUME: 19
ISSUE: 3
Year: 2021
Published on: 06 May, 2021
Page: [238 - 247]
Pages: 10
DOI: 10.2174/1570162X19666210118151249
Price: $65

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