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Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya

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 a...

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Autores principales: Wohlford, Eric M, Asito, Amolo S, Chelimo, Kiprotich, Sumba, Peter O, Baresel, Paul C, Oot, Rebecca A, Moormann, Ann M, Rochford, Rosemary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847075/
https://www.ncbi.nlm.nih.gov/pubmed/24016332
http://dx.doi.org/10.1186/1750-9378-8-34
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author Wohlford, Eric M
Asito, Amolo S
Chelimo, Kiprotich
Sumba, Peter O
Baresel, Paul C
Oot, Rebecca A
Moormann, Ann M
Rochford, Rosemary
author_facet Wohlford, Eric M
Asito, Amolo S
Chelimo, Kiprotich
Sumba, Peter O
Baresel, Paul C
Oot, Rebecca A
Moormann, Ann M
Rochford, Rosemary
author_sort Wohlford, Eric M
collection PubMed
description 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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spelling pubmed-38470752013-12-04 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 O Baresel, Paul C Oot, Rebecca A Moormann, Ann M Rochford, Rosemary Infect Agent Cancer Research Article 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. BioMed Central 2013-09-09 /pmc/articles/PMC3847075/ /pubmed/24016332 http://dx.doi.org/10.1186/1750-9378-8-34 Text en Copyright © 2013 Wohlford et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wohlford, Eric M
Asito, Amolo S
Chelimo, Kiprotich
Sumba, Peter O
Baresel, Paul C
Oot, Rebecca A
Moormann, Ann M
Rochford, Rosemary
Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
title Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
title_full Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
title_fullStr Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
title_full_unstemmed Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
title_short Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya
title_sort identification of a novel variant of lmp-1 of ebv in patients with endemic burkitt lymphoma in western kenya
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847075/
https://www.ncbi.nlm.nih.gov/pubmed/24016332
http://dx.doi.org/10.1186/1750-9378-8-34
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