Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
Wohlford, Eric M. ; Asito, Amolo S. ; Chelimo, Kiprotich ; Sumba, Peter Odada ; Baresel, Paul C. ; Oot, Rebecca A. ; Moormann, Ann M. ; Rochford, Rosemary A.
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Abstract
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.
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Wohlford EM, Asito AS, Chelimo K, Sumba PO, Baresel PC, Oot RA, Moormann AM, Rochford R. Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya. Infect Agent Cancer. 2013 Sep 9;8(1):34. doi: 10.1186/1750-9378-8-34. Link to article on publisher's site