Author SummaryAfter an initial lytic infection, many viruses establish a lifelong latent infection that hides them from the host immune system activity until reactivation. To understand the resurgence of the associated diseases, it is indispensable to acquire a better knowledge of the different mechanisms involved in the antiviral defense. During latency, viral genomes of nuclear-replicative viruses, such as herpes simplex virus type 1 (HSV-1), are stored in the nucleus of host cells in a non-integrated form. Latency establishment is associated with a drastic change in HSV-1 gene expression program that is maintained until reactivation occurs. The last two decades of research has revealed that the functional organization of the cell nucleus, so-called nuclear architecture, is a major factor of regulation of cellular genes expression. Nonetheless, the role of nuclear architecture on HSV-1 gene expression has been widely overlooked. Here we describe that the genome of HSV-1 selectively interacts with two major nuclear structures, the promyelocytic nuclear bodies (PMLNBs or ND10) and the centromeres. We provide evidence supporting that these nuclear domains directly influence the behavior of latent viral genomes and their transcriptional activity. Overall, this study demonstrates that nuclear architecture is a major parameter driving the highly complex HSV-1 latency process.
Catez, F., Picard, C., Held, K., Gross, S., Rousseau, A., Theil, D., … Lomonte, P. (2012). HSV-1 Genome Subnuclear Positioning and Associations with Host-Cell PML-NBs and Centromeres Regulate LAT Locus Transcription during Latency in Neurons. PLoS Pathogens, 8(8). https://doi.org/10.1371/journal.ppat.1002852