The analysis showed that one 25-amino acid segment within EBNA-1 was responsible for the regulation of viral gene transcription, the first step in the process by which a gene's coded information is converted first into RNA and then into protein.
Mutating the unique segment of amino acids prevented EBNA-1 from transforming resting B cells into proliferating cells.
Under normal conditions, a cellular protein binds this 25-amino acid segment of EBNA-1, allowing transcription of viral and cellular genes regulated by EBNA-1 to occur. Hammerschmidt and Sugden are now trying to identify the cellular protein.
"If we can identify this protein, it will be easier for us to develop assays to screen for small molecules that will compete with the protein in binding to EBNA-1," Sugden says. "By preventing the cellular protein from binding with the segment, EBNA-1 will not be able to carry out its function and the tumor cells it sustains will die."
The goal, which Sugden expects is achievable, is to end up with a drug that kills only EBV-positive tumor cells and doesn't harm other tissues in the body.