Title:Resveratrol Promotes HIV-1 Tat Accumulation via AKT/FOXO1 Signaling Axis and Potentiates Vorinostat to Antagonize HIV-1 Latency
Volume: 19
Issue: 3
Author(s): Zeming Feng, Zhengrong Yang, Xiang Gao, Yuhua Xue and Xiaohui Wang*
Affiliation:
- Shenzhen Center for Disease Control and Prevention, Shenzhen,China
Keywords:
HIV-1, Reservoirs, Resveratrol, HIV-1 Tat, AKT/FOXO1, P-TEFb, Super Elongation Complex.
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.
