The targeted cytosolic degradation of class I histone deacetylases is essential for efficient alphaherpesvirus replication

The precise mechanisms by which Alphaherpesviruses alter histone modifications to modulate chromatin structure remain incompletely understood. This study identifies a novel strategy employed by Alphaherpesviruses to disrupt host chromatin regulation: the MDM2-mediated K63-linked polyubiquitination and subsequent proteasomal degradation of class I histone deacetylases. Our findings represent the first demonstration of how Alphaherpesviruses exploit the MDM2-HDAC pathway to subvert host epigenetic control, thereby uncovering a promising target for the development of antiviral therapies against herpesvirus infections.