Targeting Latent HIV Reservoirs: Effectiveness of Combination Therapy with HDAC and PARP Inhibitors DOI Creative Commons

Hasset Tibebe,

Dacia Marquez,

Aidan McGraw

и другие.

Viruses, Год журнала: 2025, Номер 17(3), С. 400 - 400

Опубликована: Март 12, 2025

The “Kick and Kill” strategy, which aims to reactivate latent HIV reservoirs facilitate the clearance of reactivated HIV-infected cells, has yet achieve a functional cure due limited efficacy current latency reversal agents. This study evaluates combination histone deacetylase (HDAC) inhibitor with poly(ADP-ribose) polymerase (PARP) in immune-mediated clearance. Latently infected J-Lat cells dual-fluorescent primary CD4 T were treated HDAC (vorinostat) one four PARP inhibitors (olaparib, rucaparib, niraparib, or talazoparib). inhibitors, when administered alone, showed no activity. However, combined vorinostat, their increased threefold compared vorinostat alone. effect was mediated by inhibition tankyrase, superfamily member, modulates Hippo signaling pathway. In HIVGR670-infected reduced reservoir size 67%. addition, talazoparib alone significantly actively 50%. Talazoparib-treated peripheral blood mononuclear co-cultured K562 demonstrated enhanced NK-cell-mediated cytotoxicity, 10% reduction cell viability. These findings demonstrate that combining augments reduction. With both used this approved FDA for cancer treatment, therapy holds strong potential rapid clinical integration, contingent upon confirmation safety ongoing vivo studies.

Язык: Английский

Targeting Latent HIV Reservoirs: Effectiveness of Combination Therapy with HDAC and PARP Inhibitors DOI Creative Commons

Hasset Tibebe,

Dacia Marquez,

Aidan McGraw

и другие.

Viruses, Год журнала: 2025, Номер 17(3), С. 400 - 400

Опубликована: Март 12, 2025

The “Kick and Kill” strategy, which aims to reactivate latent HIV reservoirs facilitate the clearance of reactivated HIV-infected cells, has yet achieve a functional cure due limited efficacy current latency reversal agents. This study evaluates combination histone deacetylase (HDAC) inhibitor with poly(ADP-ribose) polymerase (PARP) in immune-mediated clearance. Latently infected J-Lat cells dual-fluorescent primary CD4 T were treated HDAC (vorinostat) one four PARP inhibitors (olaparib, rucaparib, niraparib, or talazoparib). inhibitors, when administered alone, showed no activity. However, combined vorinostat, their increased threefold compared vorinostat alone. effect was mediated by inhibition tankyrase, superfamily member, modulates Hippo signaling pathway. In HIVGR670-infected reduced reservoir size 67%. addition, talazoparib alone significantly actively 50%. Talazoparib-treated peripheral blood mononuclear co-cultured K562 demonstrated enhanced NK-cell-mediated cytotoxicity, 10% reduction cell viability. These findings demonstrate that combining augments reduction. With both used this approved FDA for cancer treatment, therapy holds strong potential rapid clinical integration, contingent upon confirmation safety ongoing vivo studies.

Язык: Английский

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