Portal de Periódicos da CAPES

An Atlas of the Epstein-Barr Virus Transcriptome and Epigenome Reveals Host-Virus Regulatory Interactions

2012; Cell Press; Volume: 12; Issue: 2 Linguagem: Inglês

10.1016/j.chom.2012.06.008

1934-6069

Aaron Arvey, Italo Tempera, Kevin Tsai, Horng-Shen Chen, Nadezhda Tikhmyanova, Michael Klichinsky, Christina Leslie, Paul M. Lieberman,

Cytomegalovirus and herpesvirus research

Summary Epstein-Barr virus (EBV), which is associated with multiple human tumors, persists as a minichromosome in the nucleus of B lymphocytes and induces malignancies through incompletely understood mechanisms. Here, we present a large-scale functional genomic analysis of EBV. Our experimentally generated nucleosome positioning maps and viral protein binding data were integrated with over 700 publicly available high-throughput sequencing data sets for human lymphoblastoid cell lines mapped to the EBV genome. We found that viral lytic genes are coexpressed with cellular cancer-associated pathways, suggesting that the lytic cycle may play an unexpected role in virus-mediated oncogenesis. Host regulators of viral oncogene expression and chromosome structure were identified and validated, revealing a role for the B cell-specific protein Pax5 in viral gene regulation and the cohesin complex in regulating higher order chromatin structure. Our findings provide a deeper understanding of latent viral persistence in oncogenesis and establish a valuable viral genomics resource for future exploration.