Quercetin Synergistically Reactivates Human Immunodeficiency Virus Type 1 Latency By Activating Nuclear Factor-Kappa B

Highly active antiretroviral therapy (HAART) is very effective in suppressing human immunodeficiency virus type 1 (HIV-1) replication. However, the treatment is required to be administered for the remainder of an individual's lifetime due to latent HIV-1 reservoirs. The 'shock-and-kill' strategy, which involves using agents to reactivate latent HIV-1 and subsequently killing latently infected cells in the presence of HAART, was recently proposed. Unfortunately, no agents have currently demonstrated an ability to reactivate latent HIV-1 in vivo in the absence of toxicity. Therefore, the identification of novel latency activators is required. In order to identify a potential novel agent, the present study investigated the effect of quercetin on latent HIV-1 reactivation using an established model of HIV-1 latency. As a marker for reactivation of HIV-1 in C11 Jurkat cells, the expression of green fluorescent protein, controlled by HIV-1 long terminal repeat, was observed by fluorescence microscopy. The results of the present study demonstrated that quercetin effectively reactivated latent HIV-1 gene expression alone, and led to synergistic reactivation when combined with prostratin or valproic acid. In addition, the present study provides evidence that quercetin may reactivate HIV-1 expression by inducing nuclear factor-kappa B nuclear translocation, and that the toxicity of quercetin is lower when compared with various additional activators of HIV-1. Combined, the results of the present study indicate that quercetin may be an effective agent to disrupt HIV-1 latency and may be useful in future eradication strategies.