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.