Epigenetic control of herpes simplex virus 1 latency Biologie des Séquences Répétées

The establishment of latent herpes simplex virus 1 (HSV-1) infection involves an intricate interplay of cellular and molecular processes. On the epigenetic front, this entails viral chromatinization and the interaction between latent episomal viral genomes and the cell's nucleus. Promyelocytic leukemia nuclear bodies (PML NBs) are nuclear membrane-less organelles responding to interferon stimuli, and playing a major role in the transcriptional regulation of HSV-1 latent genomes through an intrinsic antiviral response within the nucleus. PML NBs exhibit a dynamic protein composition due to their ability to phase separate. After HSV-1 enters the nucleus, PML NBs sequester HSV-1 genomes, histone chaperones, and chromatin modifiers, leading to the acquisition of repressive histone marks on HSV-1 genomes associated with PML NBs (also referred to as viral DNA-containing PML NBs or vDCP NBs). vDCP NBs, a significant feature of HSV-1 latency in neurons, have the capacity to maintain latent HSV-1 genomes in a transcriptionally inactive yet reversible state of quiescence. Our unpublished work unveiled the indispensable role of the HUSH (human silencing hub) complex and its effectors, SETDB1 and MORC2, in establishing and sustaining latent HSV-1 infection. In my presentation, I will delve into the epigenetic regulation of HSV-1 latency, with a specific focus on the function of the HUSH repressor complex.