The multiple membrane-spanning segments of the BNLF-1 oncogene from Epstein-Barr virus are required for transformation.

The BNLF-1 gene from Epstein-Barr virus (EBV) induces anchorage-independent and tumorigenic growth in rodent cell lines. The BNLF-1 protein (also termed LMP) is a membrane protein, and its predicted amino acid sequence indicates that the protein has six membrane-spanning segments in addition to a short amino-terminal (approximately 25 amino acids) and a long carboxyl-terminal (approximately 200 amino acids) cytoplasmic domain. To identify the regions of the protein that are essential for its transforming activity, we have constructed deletion mutants of the BNLF-1 gene and tested them for transforming activity. Surprisingly, the entire carboxyl-terminal cytoplasmic domain is dispensable for transforming activity, whereas the putative membrane-spanning segments are essential. These observations indicate that BNLF-1 has a novel function that is distinct from the functions associated with other membrane-associated viral transforming proteins. We speculate that BNLF-1 is a receptor for a growth-promoting agent, with its trans-membrane domain involved in ligand binding, and its amino-terminal domain or cytoplasmic loops involved in coupling BNLF-1 to effector molecules in the cell, a situation analogous to the rhodopsin group of receptors.