Researcher Profile

Dr. Jeffery Sample’s research focuses on the mechanisms that enable the Epstein-Barr virus (EBV), a human herpesvirus, to contribute to malignancy. He has a long history of contributions to the EBV field, particularly within the area of viral latency, which is the form of EBV infection linked to its significant oncogenic potential. Dr. Sample’s research interests have ranged from deciphering key mechanisms that regulate expression of the EBV latency-associated genes, to the specific contributions that these EBV genes make to cell transformation. Recent focus has been on the regulatory mechanisms that promote persistent latent infection within B lymphocytes, a general prerequisite for the development of EBV-associated tumors which develop years to decades following primary infection. This work has revealed that the EBV genetic locus containing the gene BHLF1 contributes to EBV latency and its associated growth-transforming properties in B lymphocytes. This was totally unexpected, as the BHLF1 gene has long been known to contribute to EBV replication and was not thought to have any role in latency. While BHLF1 can encode an EBV protein during the virus replication cycle, the RNAs expressed from this gene locus during latent infection appear to be long noncoding RNAs (lncRNAs), i.e., transcripts that act not as a template for synthesis of a polypeptide, but directly as RNA. Moreover, the protein-coding potential of this gene appears to rely on the presence of another EBV protein that, unlike BHLF1, is only expressed during virus replication. Thus, BHLF1 appears to be a rare EBV gene that functions during both virus replication and latent infection, albeit through different mechanisms. This is the first observation that a lncRNA-coding locus plays a critical role in EBV latency, and work is underway to define the mechanisms through which BHLF1 contributes to EBV latency and its associated oncogenic potential.