دورية أكاديمية
أعرض في EDS

Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice.

التفاصيل البيبلوغرافية
العنوان: Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice.
المؤلفون: Arandjelovic P; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia., Kim Y; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Cooney JP; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia., Preston SP; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia., Doerflinger M; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia., McMahon JH; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC, Australia., Garner SE; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia., Zerbato JM; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Roche M; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Emerging Infections Program, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia., Tumpach C; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Ong J; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Sheerin D; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia., Smyth GK; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia., Anderson JL; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Allison CC; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia., Lewin SR; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC, Australia; Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Pellegrini M; Division of Infectious Disease and Immune Defence, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia. Electronic address: pellegrini@wehi.edu.au.
المصدر: Cell reports. Medicine [Cell Rep Med] 2023 Sep 19; Vol. 4 (9), pp. 101178. Date of Electronic Publication: 2023 Aug 30.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: HIV-1* , HIV Seropositivity*, Humans ; Animals ; Mice ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Disease Models, Animal
مستخلص: HIV-1 persists indefinitely in people living with HIV (PLWH) on antiretroviral therapy (ART). If ART is stopped, the virus rapidly rebounds from long-lived latently infected cells. Using a humanized mouse model of HIV-1 infection and CD4 + T cells from PLWH on ART, we investigate whether antagonizing host pro-survival proteins can prime latent cells to die and facilitate HIV-1 clearance. Venetoclax, a pro-apoptotic inhibitor of Bcl-2, depletes total and intact HIV-1 DNA in CD4 + T cells from PLWH ex vivo. This venetoclax-sensitive population is enriched for cells with transcriptionally higher levels of pro-apoptotic BH3-only proteins. Furthermore, venetoclax delays viral rebound in a mouse model of persistent HIV-1 infection, and the combination of venetoclax with the Mcl-1 inhibitor S63845 achieves a longer delay in rebound compared with either intervention alone. Thus, selective inhibition of pro-survival proteins can induce death of HIV-1-infected cells that persist on ART, extending time to viral rebound.
Competing Interests: Declaration of interests The Walter and Eliza Hall Institute receives milestone and royalty payments related to venetoclax and has a commercial collaboration with Servier with respect to Mcl-1 inhibitors under which it may receive future payments. M.P. is eligible for financial benefits related to these payments. S.R.L. has received investigator-initiated, industry-funded research support from Merck Sciences, Gilead Sciences, and ViiV and provision of reagents from Infinity Pharmaceuticals, Merck Sciences, and BMS for investigator-initiated research. S.R.L. and J.L.A. have research collaborations with Merck Sciences unrelated to this work.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: UM1 AI164560 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (S63845)
N54AIC43PW (venetoclax)
0 (Bridged Bicyclo Compounds, Heterocyclic)
تواريخ الأحداث: Date Created: 20230831 Date Completed: 20230922 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10518630
DOI: 10.1016/j.xcrm.2023.101178
PMID: 37652018
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2023.101178