HIV Tat as a latency reversing agent: turning the tables on viral persistence

Abstract

The ‘shock and kill’ approach to an HIV cure involves the use of latency reversing agents (LRAs) to reactivate latent HIV, with the aim to induce death of infected cells through virus induced cytolysis or immune mediated clearance. Most LRAs tested to date have been unable to overcome the blocks to transcription elongation and splicing that persist in resting CD4+ T cells. Furthermore, most LRAs target host factors and therefore have associated toxicities. Therefore, there remains a high need for HIV-specific LRAs that can also potently upregulate expression of multiply-spliced HIV RNA and viral protein. The HIV Transactivator of Transcription (Tat) protein plays an important role in viral r..