Journal of agricultural and food chemistry 2017 05 04() doi 10.1021/acs.jafc.7b00418
The persistence of latent HIV reservoirs presents significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression while its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Modes of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homolog 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under the co-treatment with resveratrol and conventional LRAs. Collectively, our research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.