Epstein–Barr virus oncoprotein–driven B cell metabolism remodeling
Eric Burton, Benjamin E. Gewurz
Abstract
The -herpesvirus Epstein-Barr virus (EBV) persistently infects >95% of adults worldwide and contributes to 200,000 cancers annually EBV uses latency programs to convert metabolically quiescent B lymphocytes into blasts that enter germinal centers and differentiate into memory B cells, the reservoir for lifelong infection. Over the first 3 days of infection, EBV expresses the pre-proliferation program, where particularly high levels of Epstein-Barr nuclear antigen 2 (EBNA2) and its key host target MYC induce metabolism pathways needed for B cell remodeling and proliferation (Fig Over this period, infected cells quadruple in volume in preparation for hyperproliferation The EBV latency IIb program, comprised of 6 EBNAs and noncoding RNA (ncRNA), then supports hyperproliferation between days 4 and 7 postinfection in cell culture (Fig 1). Subsequently, cells convert to lymphoblastoid physiology, where 6 EBNAs and 2 latent membrane proteins (LMPs) further remodel host metabolism [7,8]. If left unchecked by immune surveillance, latency III causes outgrowth of lymphoblastoid cell lines (LCLs) that model posttransplant lymphoproliferative diseases (PTLDs) and central nervous system lymphomas [1] (Fig 1). Here, we review key host metabolism pathways subverted by EBV oncoproteins, with a focus on B cell transformation.