Noncanonical-NF-κB activation and DDX3 inhibition reduces the HIV-1 reservoir by elimination of latently infected cells ex-vivo .

Autor:	Jansen J; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam , Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity , Amsterdam, the Netherlands., Kroeze S; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam , Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity , Amsterdam, the Netherlands., Man S; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam , Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity , Amsterdam, the Netherlands., Andreini M; First Health Pharmaceuticals B.V , Amsterdam, the Netherlands., Bakker J-W; First Health Pharmaceuticals B.V , Amsterdam, the Netherlands., Zamperini C; First Health Pharmaceuticals B.V , Amsterdam, the Netherlands., Tarditi A; First Health Pharmaceuticals B.V , Amsterdam, the Netherlands., Kootstra NA; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam , Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity , Amsterdam, the Netherlands., Geijtenbeek TBH; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam , Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity , Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2024 Jan 11; Vol. 12 (1), pp. e0318023. Date of Electronic Publication: 2023 Dec 05.
DOI:	10.1128/spectrum.03180-23
Abstrakt:	Importance: HIV-1 continues to be a major global health challenge. Current HIV-1 treatments are effective but need lifelong adherence. An HIV-1 cure should eliminate the latent viral reservoir that persists in people living with HIV-1. Different methods have been investigated that focus on reactivation and subsequent elimination of the HIV-1 reservoir, and it is becoming clear that a combination of compounds with different mechanisms of actions might be more effective. Here, we target two host factors, inhibitor of apoptosis proteins that control apoptosis and the DEAD-box helicase DDX3, facilitating HIV mRNA transport/translation. We show that targeting of these host factors with SMAC mimetics and DDX3 inhibitors induce reversal of viral latency and eliminate HIV-1-infected cells in vitro and ex vivo . Competing Interests: M.A., J.B., C.Z., and A.T. are employees of First Health Pharmaceuticals B.V.
Databáze:	MEDLINE
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