title: As2O3 synergistically reactivate latent HIV-1 by induction of NF-κB.
abstract: 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.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.forename: Xiying
authors.initials: X
authors.lastname: Qu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhu
authors.forename: Hanxian
authors.initials: H
authors.lastname: Zeng
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects*
chemical_list: D001152:Arsenicals; D016328:NF-kappa B; D010087:Oxides; D010703:Phorbol Esters; D014409:Tumor Necrosis Factor-alpha; C070999:prostratin; D014635:Valproic Acid; D001241:Aspirin; D000077237:Arsenic Trioxide