ATRX limits the accessibility of histone H3-occupied HSV genomes during lytic infection

• DOI: 10.1371/journal.ppat.1009567
• Publication Date: 2021-04-28T20:58:29Z
• Authors: Joseph M. Cabral; Camille H. Cushman; Catherine N. Sodr...; David M. Knipe
• Keywords: ATRX; Death-associated protein 6; Lytic cycle

Histones are rapidly loaded on the HSV genome upon entry into nucleus of human fibroblasts, but effects histone loading viral replication have not been fully defined. We showed recently that ATRX is dispensable for de novo deposition H3 to genomes after nuclear restricted infection through maintenance heterochromatin. To further investigate roles and other chaperones play in restriction HSV, we infected fibroblasts were systematically depleted chaperones. found ATRX/DAXX complex unique among its capacity restrict ICP0-null infection. Only depletion significantly alleviated replication. Interestingly, no individual chaperone was required onto input genomes, suggesting during lytic infection, may occur multiple pathways. ChIP-seq total control ATRX-KO cells with DNA high levels histones across entire genome. Despite H3, ATAC-seq analysis revealed highly accessible, especially regions GC content, organized largely ordered nucleosomes reduced accessibility activity a TN5 transposase enhanced accumulation fragment sizes associated nucleosome-like structures. Together, these findings support model which restricts by altering structure H3-loaded chromatin reduces transcription. High rich genome, S component inverted repeats HSV-1 show increased accessibility, lead ability transcribe IE genes encoded initiation