September 25, 2019
Our laboratory studies the mechanisms by which Epstein-Barr Virus (EBV) promotes the proliferation and immortalization of human B cells as a model for lymphomas of the immune suppressed. EBV does this through expression of a set of viral latency proteins and non-coding RNAs, which are sufficient to drive resting B cells to proliferate and grow in culture indefinitely. We have studied the nature of this proliferative signal, the metabolic requirements, and the survival functions altered by the virus during the process of B-cell outgrowth. We have identified the DNA damage response as a critical sensor of metabolic stress that results from viral-induced hyper-proliferation during the early stage of infection. Most infected cells fail to be immortalized due to this response, but those that do survive become lymphoblastoid cell lines (LCLs), which upregulate signaling pathways and metabolic programs found in activated B cell lymphomas. Our studies have defined molecular circuits that underlie the transition from uninfected resting mature B cells to EBV-infected LCLs as a model for the characterization of and identification of therapeutic targets in B-cell lymphomas.