Abstract
Background: Current antiretroviral therapy (ART) cannot cure HIV-1 infection due to the presence of latent viral reservoirs. The “shock and kill” strategy is a promising approach to eliminate the viral reservoir. However, there are various limits existing in current latency-reversing agents, searching for new activators are urgently needed.
Objective: The present study aimed at investigating the ability of hymecromone and scoparone for activating HIV-1 from latent reservoirs.
Methods: Jurkat T cell model of HIV-1 latently were used to evaluate the effect of hymecromone and scoparone. The percentage of green florescence protein expression as a marker for reactivation of HIV-1 promoter was measured via FACScan. The expression of CD25 and CD69 in human peripheral blood mononuclear cells was measured by flow cytometry at 72 h post-treatment with hymecromone or scoparone or prostratin using antibodies against CD25 and CD69.
Results: Hymecromone and scoparone can induce HIV-1 LTR reactivation in a dose and timedependent. We further show that hymecromone and scoparone can reactivate latent virus without inducing the activation of global T cells. We also found that scoparone acts by NF-&kgr;B signal pathway.
Conclusion: Hymecromone and scoparone can effectively reactivate latent HIV-1 with low cellular toxicity, indicating hymecromone and scoparone might be potential drugs for HIV-1 reservoir eradication strategies in the future.
Keywords: Coumarin compounds, hymecromone, scoparone, HIV-1 latency, reactivation.
Graphical Abstract