A truncated HIV Tat demonstrates potent and specific latency reversal activity.
Antimicrob Agents Chemother
; 67(11): e0041723, 2023 11 15.
Article
em En
| 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latent reservoir is capable of producing replication-competent infectious viruses once prolonged suppressive cART is withdrawn.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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Viral
/
Infecções por HIV
/
HIV-1
/
Produtos do Gene tat do Vírus da Imunodeficiência Humana
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article