The involvement of DSIF in HIV transcription and viral latency.

Antiretroviral therapy has significantly improved the survival of individuals infected with the human immunodeficiency virus (HIV). Yet, a complete cure remains out of sight, as latent HIV infection persists in a cell reservoir that is long-lived and resistant to treatment. Since HIV latency is established primarily at the step of proviral transcription repression, we have been studying the role of the host elongation machinery and RNA Polymerase II (RNAPII) in controlling HIV transcription elongation and viral latency.

DRB Sensitivity Inducing Factor (DSIF) is a pausing inducing factor that consists of Spt4 and Spt5 subunits, and together with Negative Elongation Factor (NELF) repress transcription elongation in metazoan, by inducing RNAPII pausing at promoter proximal sites. To release RNAPII from its pause, Super Elongation Complex (SEC) and the Positive Transcription Elongation Factor b (P-TEFb) join functions and enhance transcription elongation by phosphorylating NELF/RD, Spt5, and the long C-terminal domain (CTD) of RNAPII, turning the Spt5 from an inhibitor to an activator of transcription elongation.

This study aimed to better understand the role of DSIF regulating HIV latency. To this aim, we depleted Spt5 and Spt4 subunits in HIV infected cells and monitored effects on HIV gene transcription and viral latency. We will discuss ongoing work that highlights preliminary results on the role of DSIF, exploring its role in modulating viral latency. Our work will open new insights on HIV gene expression and viral latency, and will have an impact on understanding the role of this complex in eukaryotic gene transcription.

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