VZV BioID
Varicella-zoster virus (VZV) establishes lifelong latency in sensory ganglia, but the molecular basis of latency and reactivation remains ill-understood. We previously showed that latent VZV transcription is restricted to the VZV latency-associated transcript (VLT) and VLT-ORF63, encoding VLT protein (pVLT) and the fusion protein pVLT-ORF63. Here, we investigated the functions of pVLT, pVLT-ORF63 and pORF63 during lytic infection of human ARPE-19 cells. Biotin-proximity labelling identified host chromatin-remodelling factors, especially the SIN3A/HDAC complex, as interactors of pVLT-ORF63 and pORF63, whereas few interactions were detected for pVLT. Functionally, pORF63, but not pVLT-ORF63, increased HDAC activity in a SIN3A-dependent manner. Although both proteins reduced H3K27ac without globally altering histone acetylation, CUT&RUN profiling revealed that only pORF63 redistributed SIN3A and increased H3K4me3 at selected promoters. Together, these findings establish pORF63 and pVLT-ORF63 as modulators of host chromatin, with largely discrete functions that could regulate cellular and viral transcription during lytic infection and reactivation from latency.