Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
1 Center for Global Health and Translational Science, SUNY Upstate Medical University, Syracuse, NY 13210, USA
2 Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
3 Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya
4 Department of Bomedical Science and Technology, Maseno University, Maseno, Kenya
5 Department of Pediatrics, University of Massachusetts Medical School, Worchester, MA 01655, USA
Infectious Agents and Cancer 2013, 8:34 doi:10.1186/1750-9378-8-34Published: 9 September 2013
Epstein Barr virus (EBV) is a gammaherpesvirus that is associated with nasopharyngeal carcinoma (NPC) and endemic Burkitt lymphoma (eBL). EBV carries several latent genes that contribute to oncogenesis including the latent membrane protein 1 (LMP-1), a known oncogene and constitutively active CD40 homolog. Variation in the C terminal region of LMP-1 has been linked to NPC pathogenesis, but little is known regarding LMP-1 variation and eBL.
In the present study, peripheral blood samples were obtained from 38 eBL patients and 22 healthy controls in western Kenya, where the disease is endemic. The LMP-1 C-terminal region from these samples was sequenced and analyzed. The frequency of a 30 base pair deletion of LMP-1 previously linked to NPC was not associated with eBL compared to healthy controls. However a novel LMP-1 variant was identified, called K for Kenya and for the G318K mutation that characterizes it. The K variant LMP-1 was found in 40.5% of eBL sequences and 25.0% of healthy controls. All K variant sequences contained mutations in both of the previously described minimal T cell epitopes in the C terminal end of LMP-1. These mutations occurred in the anchor residue at the C-terminal binding groove of both epitopes, a pocket necessary for MHC loading.
Overall, our results suggest that there is a novel K variant of LMP-1 in Kenya that may be associated with eBL. Further studies are necessary to determine the functional implications of the LMP-1 variant on early events in eBL genesis.