A truncated HIV Tat demonstrates potent and specific latency reversal activity
Van Gulck, E.; Pardons, M.; Nijs, E.; Verheyen, N.; Dockx, K.; Van Den Eynde, C.; Battivelli, E.; Vega, J.; Florence, E.; Autran, B.; Archin, N.; Margolis, D. M.; Katlama, C.; Hamimi, C.; Van Den Wyngaert, I.; Eyassu, F.; Vandekerckhove, L.; Boden, D.
Show 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This latent reservoir is capable of producing replication-competent infectious virus once prolonged suppressive cART is withdrawn.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 will likely 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 nor any significant transcriptome perturbation.
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