The role of Tat in HIV latency and reactivation

David M MargolisEdward P Browne^*

• The University of North Carolina at Chapel Hill Institute for Global Health and Infectious Diseases, Chapel Hill, United States

A latent reservoir of HIV-infected cells in which viral antigen expression undetected is the primary barrier to a cure. To sensitize this reservoir in people with HIV (PWH) on antiretroviral therapy (ART) to elimination, latency reversing agents (LRAs) have been tested, but appear typically inefficient at promoting broad reservoir reactivation. More potent and selective tools for latency reversal are needed. Recently, delivery of mRNA encoding the viral protein Tat, which promotes transcriptional elongation, has attracted interest as a possible HIV-specific approach to inducing latency reversal. This review will cover the evidence that Tat plays a key role in both establishment of HIV latency and latency reversal, as well as recent developments in which Tat mRNA delivery has been used to enhance latency reversal approaches. Delivery of Tat to infected cells represents a promising avenue to bypass the limitations of small molecule LRAs and achieve broad reactivation of the clinical reservoir.