An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions.
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.
Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Aaron
A
Arvey
Italo
I
Tempera
Kevin
K
Tsai
Horng-Shen
HS
Chen
Nadezhda
N
Tikhmyanova
Michael
M
Klichinsky
Christina
C
Leslie
Paul M
PM
Lieberman
D057890:Epigenomics; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D014764:Viral Proteins