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• W4309758346 abstract "Abstract Combinational antiretroviral therapy (cART) effectively suppresses HIV-1 infection, replication, and pathogenesis in HIV-1 patients. However, the patient’s HIV-1 reservoir still cannot be eliminated by current cART or other therapies. One putative HIV-1 eradication strategy is “shock and kill”, which reactivates HIV-1 in latently-infected cells and induces their cytopathic effect or immune clearance to decrease the patients’ reservoir size. KDM5A and KDM5B act as the HIV-1 latency-promoting genes, decreasing the HIV-1 viral gene transcription and reactivation in infected cells. Depletion of KDM5 A/B by siRNA knockdown (KD) increases H3K4 trimethylation (H3K4me3) in HIV-1 Tat-mediated transactivation. We also found that the KDM5-specific inhibitor JQKD82 can increase H3K4me3 at the HIV-1 LTR region during HIV-1 reactivation and induce cytopathic effects. We applied the JQKD82 in combination with the non-canonical NF-κB activator AZD5582, which synergistically induced HIV-1 reactivation and cell apoptosis in HIV-1 infected cells. These results suggested that the KDM5 inhibition can be a putative HIV-1 latency-reversing strategy for the HIV-1 “shock and kill” eradication therapy." @default.
• W4309758346 created "2022-11-29" @default.
• W4309758346 creator A5005192531 @default.
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• W4309758346 date "2022-11-17" @default.
• W4309758346 modified "2023-10-16" @default.
• W4309758346 title "KDM5A/B promotes HIV-1 latency and KDM5 inhibitors promote HIV-1 lytic reactivation" @default.
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