A truncated HIV Tat demonstrates potent and specific latency reversal activity
A major barrier to HIV-1 cure is caused by the pool of latently infected CD4 T-cells that persist under combination antiretroviral therapy (cART). This latent reservoir is capable of producing replication-competent infectious viruses once prolonged suppressive cART is withdrawn. Inducing the reactivation of HIV-1 gene expression in T-cells harboring a latent provirus in people living with HIV-1 under cART may result in depletion of this latent reservoir due to cytopathic effects or immune clearance. Studies have investigated molecules that reactivate HIV-1 gene expression, but to date, no latency reversal agent has been identified to eliminate latently infected cells harboring replication-competent HIV in cART-treated individuals. Stochastic fluctuations in HIV-1 tat gene expression have been described and hypothesized to allow the progression into proviral latency. We hypothesized that exposing latently infected CD4+ T-cells to Tat would result in effective latency reversal. Our results indicate the capacity of a truncated Tat protein and mRNA to reactivate HIV-1 in latently infected T-cells ex vivo to a similar degree as the protein kinase C agonist: phorbol 12-myristate 13-acetate, without T-cell activation or any significant transcriptome perturbation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Antimicrobial agents and chemotherapy - 67(2023), 11 vom: 15. Nov., Seite e0041723 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Van Gulck, Ellen [VerfasserIn] |
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| Links: |
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| Themen: |
HIV |
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| Anmerkungen: |
Date Completed 29.12.2023 Date Revised 10.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/aac.00417-23 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM363665773 |
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| 245 | 1 | 2 | |a A truncated HIV Tat demonstrates potent and specific latency reversal activity |
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| 520 | |a A major barrier to HIV-1 cure is caused by the pool of latently infected CD4 T-cells that persist under combination antiretroviral therapy (cART). This latent reservoir is capable of producing replication-competent infectious viruses once prolonged suppressive cART is withdrawn. Inducing the reactivation of HIV-1 gene expression in T-cells harboring a latent provirus in people living with HIV-1 under cART may result in depletion of this latent reservoir due to cytopathic effects or immune clearance. Studies have investigated molecules that reactivate HIV-1 gene expression, but to date, no latency reversal agent has been identified to eliminate latently infected cells harboring replication-competent HIV in cART-treated individuals. Stochastic fluctuations in HIV-1 tat gene expression have been described and hypothesized to allow the progression into proviral latency. We hypothesized that exposing latently infected CD4+ T-cells to Tat would result in effective latency reversal. Our results indicate the capacity of a truncated Tat protein and mRNA to reactivate HIV-1 in latently infected T-cells ex vivo to a similar degree as the protein kinase C agonist: phorbol 12-myristate 13-acetate, without T-cell activation or any significant transcriptome perturbation | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Nijs, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Verheyen, Nick |e verfasserin |4 aut | |
| 700 | 1 | |a Dockx, Koen |e verfasserin |4 aut | |
| 700 | 1 | |a Van Den Eynde, Christel |e verfasserin |4 aut | |
| 700 | 1 | |a Battivelli, Emilie |e verfasserin |4 aut | |
| 700 | 1 | |a Vega, Jerel |e verfasserin |4 aut | |
| 700 | 1 | |a Florence, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Autran, Brigitte |e verfasserin |4 aut | |
| 700 | 1 | |a Archin, Nancie M |e verfasserin |4 aut | |
| 700 | 1 | |a Margolis, David M |e verfasserin |4 aut | |
| 700 | 1 | |a Katlama, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Hamimi, Chiraz |e verfasserin |4 aut | |
| 700 | 1 | |a Van Den Wyngaert, Ilse |e verfasserin |4 aut | |
| 700 | 1 | |a Eyassu, Filmon |e verfasserin |4 aut | |
| 700 | 1 | |a Vandekerckhove, Linos |e verfasserin |4 aut | |
| 700 | 1 | |a Boden, Daniel |e verfasserin |4 aut | |
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