Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription

Background: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell. The virus will either actively replicate to promote dissemination in blood and tissues, or become dormant mostly in memory CD4+ T cells, as part of a small but long-living latent reservoir, the main obstacle for HIV eradication. Objective: In this review, we summarize recent advances in the understanding of the multi-step mechanism that regulates Tat-mediated HIV-1 transcription and RNA polymerase II release, to promote viral transcription elongation. Early events of the human transcription elongation factor b release from the inhibitory 7SK small nuclear ribonucleoprotein complex and its recruitment to the HIV promoter will be discussed. Specific roles of the super elongation complex subunits during transcription elongation, and insight on recently identified cellular factors and mechanisms regulating HIV latency will be detailed. Conclusion: Understanding the complexity of HIV transcriptional regulation by host factors may open the door for development of novel strategies to eradicate the resilient latent reservoir.