A truncated HIV Tat demonstrates potent and specific latency reversal activity.
Antimicrob Agents Chemother
; 67(11): e0041723, 2023 11 15.
Article
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| MEDLINE
| ID: mdl-37874295
ABSTRACT
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latent reservoir is capable of producing replication-competent infectious viruses once prolonged suppressive cART is withdrawn.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.
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Base de datos:
MEDLINE
Asunto principal:
Activación Viral
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Infecciones por VIH
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VIH-1
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Productos del Gen tat del Virus de la Inmunodeficiencia Humana
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2023
Tipo del documento:
Article