Human immunodeficiency virus (HIV)

Role of UHRF1 in HIV-1 transcriptional repression through epigenetic and non-epigenetic mechanisms

Studying the molecular mechanisms that drive HIV-1 into latency is critical for targeted HIV cure efforts aiming at either reactivating or blocking viral expression. We have recently reported the involvement of the cellular epigenetic integrator UHRF1 (Ubiquitin-like with PHD and RING finger domain 1) in the epigenetic control of HIV-1 latency (Verdikt et al., 2022, eBioMedicine). Currently, we further characterized the epigenetic mechanisms of UHRF1-mediated silencing of HIV-1 and we demonstrated a non-epigenetic function of UHRF1 in HIV-1 transcription repression.

Functional role of an intragenic enhancer in HIV-1 transcription and replication

Despite numerous publications, including ours, that have provided extended knowledge about HIV-1 transcriptional regulation and latency, HIV-1 infection remains a major health issue due to the persistence of latent HIV-1 into cellular and tissue reservoirs in seropositive patients under cART. Based on this relative failure, the presence of an intragenic enhancer in the HIV-1 proviral genome could be an advantage used by HIV-1 to facilitate its replication and persistence in different cell types that can present various activation states, a feature already observed in other retroviruses. In addition, since the pool of transcription factors varies both temporally and spatially, the presence of clustered binding sites, as observed in the IRR for AP-1, PU-1 and YY1, could represent an important viral strategy to ensure HIV- 1 replication and persistence in several cellular contexts . Therefore, we believe that the HIV-1 IRR is of high importance to control viral replication levels in vivo in the two major targets of HIV-1 infection corresponding to T- lymphocytes and monocytes/macrophages.