As2O3 synergistically reactivate latent HIV-1 by induction of NF-κB.

None of the current agents can safely and effectively eliminate latent HIV-1 reservoirs, meaning that there is a major barrier to the final cure of AIDS. Arsenic trioxide (As2O3), a drug used to treat acute promyelocytic leukemia (APL), was reported to affect the transcription factors and pathways involved in modulating HIV-1 expression. However, little is known about the effect and molecular basis of As2O3 in inducing HIV-1 expression in latently infected cells. Using the Jurkat T cell model of HIV-1 latency, we found that As2O3 activated latent HIV-1 replication with a similar potency to valproic acid (VPA) and did so in a dose- and time-dependent manner. We also found that As2O3 synergistically reactivated latent HIV-1 transcription with prostratin, tumor necrosis factor alpha (TNF-α) or VPA. Moreover, we provide evidence indicating that As2O3-induced HIV-1 activation involves the nuclear factor kappa B (NF-κB) signaling pathway. In conclusion, we have found that As2O3 can synergistically reactivate latent HIV-1 with other activators, which may provide a new tool to unravel the mechanisms of virus latency and reactivation.