Journal Article

Tridimensional infiltration of DNA viruses into the host genome shows preferential contact with active chromatin

Lavigne, Marc, Marbouty, Martial, Koszul, Romain, Neuveut, Christine, Cairo, Stefano, Palumbo, Gianna Aurora, Cournac, Axel, Thierry, Agnes, Mortaza, Shogofa, Moreau, Pierrick

2018

Overview

Whether non-integrated viral DNAs distribute randomly or target specific positions within the higher-order architecture of mammalian genomes remains largely unknown. Here we use Hi-C and viral DNA capture (CHi-C) in primary human hepatocytes infected by either hepatitis B virus (HBV) or adenovirus type 5 (Ad5) virus to show that they adopt different strategies in their respective positioning at active chromatin. HBV contacts preferentially CpG islands (CGIs) enriched in Cfp1 a factor required for its transcription. These CGIs are often associated with highly expressed genes (HEG) and genes deregulated during infection. Ad5 DNA interacts preferentially with transcription start sites (TSSs) and enhancers of HEG, as well as genes upregulated during infection. These results show that DNA viruses use different strategies to infiltrate genomic 3D networks and target specific regions. This targeting may facilitate the recruitment of transcription factors necessary for their own replication and contribute to the deregulation of cellular gene expression. Whether DNA viruses contact specific regions of host genomes or make random contacts is unclear. Here, the authors use Hi-C and show that HBV cccDNA and Ad5 DNA contact preferentially active chromatin at CpG islands for the former and at transcription start sites and enhancers for the latter.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 49/15 / 49/47 / 631/326/596/1278 / 631/326/596/1550 / 631/326/596/2557 / 631/337/100 / Base Sequence / Chromatin / Chromatin - metabolism / CpG islands / CpG Islands - genetics / Deoxyribonucleic acid / Deregulation / DNA / DNA viruses / DNA, Viral - genetics / Enhancers / Gene expression / Gene Expression Regulation / Genes / Genome, Human / Genomes / Hep G2 Cells / Hepatitis B / Hepatitis B virus - physiology / Hepatocytes / Hepatocytes - virology / Humanities and Social Sciences / Humans / Infiltration / Life Sciences / Microbiology and Parasitology / Models, Biological / multidisciplinary / Plasmids - metabolism / Science / Science (multidisciplinary) / Trans-Activators - metabolism / Transcription factors / Transcription Initiation Site / Transcription, Genetic / Up-Regulation - genetics / Viral Regulatory and Accessory Proteins / Virology / Viruses