Characterization of the BNLF-1 Oncogene of Epstein-Barr Virus

Abstract

Epstein-Barr virus (EBV) is a human herpesvirus that is causally associated with several malignancies including nasopharyngeal carcinoma, African Burkitt’s lymphoma, and lymphoproliferative disorders in immunosuppressed people (reviewed in Miller 1985). In vitro EBV infects human B cells and immortalizes between 10%-100% of them (Sugden and Mark 1977; reviewed in zur Hausen 1981). It seems likely that EBV’s capacity to immortalize cells in culture is related to its tumorigenicity in vivo. This likelihood has led researchers to study the mechanism of immortalization of B cells by this virus. The EBV genes required to initiate and/or to maintain the immortalized state in vitro have not been identified. However, at least eight viral genes are found to be transcribed consistently in B cells immortalized in vitro, and circumstantial evidence exists that at least several of these gene products will be required for this process (reviewed in Knutson and Sugden 1988). Until recently, there was no evidence that causally linked any one of these eight viral genes with changes in the growth control of EBV-infected cells. It has now been shown that one viral gene, BNLF-1 (or LMP), when expressed from either of two heterologous promoters and introduced into either of two established rodent cell lines, Rat-1 (Wang et al. 1985) or BALB/3T3 cells (Baichwal and Sugden 1988), induces these cells to grow in an anchorage-independent fashion in agarose.