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Atlas of the Epstein-Barr Virus Can Help Chart the Viral Paths Toward Cancer

The Epstein-Barr virus is a remarkable virus not only for its ubiquity (nearly every adult human on Earth has been infected by it) but also because of how it evolved to become, in a sense, part of us.

As a long-term, latent infection, Epstein-Barr—or EBV, as it is known—transforms from a free-ranging virus into something much like a minichromosome, nestling among our own chromosomes in the nucleus of the cells it infects. Hidden in our B cells (the white blood cells that produce antibodies) and the epithelial cells that line our throats, sinuses, and guts, the EBV minichromosome makes use of the same molecular machines our own cells use to replicate and read our own DNA.

Unfortunately, those interactions between EBV and our own DNA can also lead to cancer. EBV is thought to be responsible for nearly one percent of all human cancers cases, including instances of B cell lymphomas, gastric carcinomas, and nasopharyngeal carcinomas.

To explore the molecular paths that allow an EBV infection to turn its host cell cancerous, researchers need a good map. Fortunately,  researchers from The Wistar Institute and Memorial Sloan-Kettering Cancer Center have teamed to publish the first annotated atlas of the Epstein-Barr virus genome, creating the most comprehensive study of how the viral genome interacts with its human host during a latent infection.

The atlas is designed to guide researchers toward new means of creating therapies against EBV-latent infection and the cancers associated with latent EBV infection, such as B cell lymphomas, gastric carcinomas, and nasopharyngeal carcinomas. The project provides the best look yet at how EBV interacts with the genes and proteins of its host cells.

As a supplement to the EBV genome—the characterization of the virus’s genes—the atlas describes the epigenome—all the protein and chemical decorations added to the EBV DNA that get passed along to new copies of the EBV virus–and the transcriptome—the catalog of all the RNA transcripts created from EBV DNA, which are either coded into protein or serve to regulate DNA directly.  The researchers discovered numerous new points of interaction between viral DNA and its host, highlighting the extensive coevolution of the virus and pointing toward possible targets for future cancer and anti-viral drugs.

The published report is available online now through the journal Cell Host & Microbe.

“Epstein-Barr is a human tumor virus associated with many carcinomas and lymphomas and how it is regulated is something we need to understand in detail,” said Paul Lieberman, Ph.D., the McNeil Professor of Molecular Medicine and Translational Research and director of Wistar’s Center for Chemical Biology and Translational Medicine. “The EBV atlas is an instructive guide for how to analyze an entire, intact genome.”