HSV-1 Genome Subnuclear Positioning and Associations with Host-Cell PML-NBs and Centromeres Regulate LAT Locus Transcription during Latency in Neurons

• DOI: 10.1371/journal.ppat.1002852
• Publication Date: 2012-08-09T21:22:23Z
• Authors: Frédéric Catez; Christel Picard; Kathrin Held; Sylvain Gross; Antoine Rousseau; Diethilde Theil; Nancy Sawtell; Marc Labetoulle; Patrick Lomonte
• Keywords: Death-associated protein 6; Virus latency; Lytic cycle; Promyelocytic leukemia protein

Major human pathologies are caused by nuclear replicative viruses establishing life-long latent infection in their host. During latency the genomes of these intimately interacting with cell nucleus environment. A hallmark herpes simplex virus type 1 (HSV-1) establishment is shutdown lytic genes expression and concomitant induction associated (LAT) transcripts. Although setting up maintenance genetic program most likely dependent on a subtle interplay between viral factors, this remains uninvestigated. Combining use situ fluorescent-based approaches high-resolution microscopic analysis, we show that HSV-1 adopt specific patterns sensory neurons latently infected mice (28 days post-inoculation, d.p.i.). Latent display two major patterns, called "Single" "Multiple", which associate centromeres, promyelocytic leukemia bodies (PML-NBs) as DNA-containing PML-NBs (DCP-NBs). 3D-image reconstruction DCP-NBs shows PML forms shell around Daxx ATRX, partners within PML-NBs. (6 d.p.i.), mouse TGs display, at level whole TG individual cells, substantial increase amount consistent interferon-mediated antiviral role PML. "Multiple" reminiscent low high-viral genome copy-containing neurons. We LAT significantly favored pattern, underlines heterogeneity copy number, pattern acquisition, association domains. Infection PML-knockout demonstrates PML/PML-NBs involved negatively regulate LAT. This study domains including centromeres functionally control latency, represent key host/virus interaction.