A truncated HIV Tat demonstrates potent and specific latency reversal activity

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.02.530914v1?rss=1 Authors: 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. 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This latent reservoir is capable of producing replication-competent infectious virus once prolonged suppressive cART is withdrawn.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. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC