{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:18Z","timestamp":1791561018611,"version":"4.3.4"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US National Institute of Health, National Cancer Institute","award":["R01 CA189806"],"award-info":[{"award-number":["R01 CA189806"]}]},{"name":"DELTAS Africa grant","award":["DEL-15-007"],"award-info":[{"award-number":["DEL-15-007"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Endemic Burkitt lymphoma (eBL) is a fast-growing germinal center B cell lymphoma, affecting 5\u201310 per 100,000 children annually, in the equatorial belt of Africa. We hypothesize that co-infections with <jats:italic>Plasmodium falciparum<\/jats:italic> (<jats:italic>Pf<\/jats:italic>) malaria and Epstein-Barr virus (EBV) impair host natural killer (NK) and T cell responses to tumor cells, and thus increase the risk of eBL pathogenesis. NK cell education is partially controlled by killer immunoglobulin-like receptors and variable expression of KIR3DL1 has been associated with other malignancies. Here, we investigated whether KIR3D-mediated mechanisms contribute to eBL, by testing for an association of <jats:italic>KIR3DL1<\/jats:italic>\/<jats:italic>KIR3DS1<\/jats:italic> genotypes with the disease in 108 eBL patients and 99 healthy Kenyan children. <jats:italic>KIR3DL1<\/jats:italic> allelic typing and EBV loads were assessed by PCR. We inferred previously observed phenotypes from the genotypes. The frequencies of <jats:italic>KIR3DL1<\/jats:italic>\/<jats:italic>KIR3DL1<\/jats:italic> and <jats:italic>KIR3DL1<\/jats:italic>\/<jats:italic>KIR3DS1<\/jats:italic> did not differ significantly between cases and controls. Additionally, none of the study participants was homozygous for <jats:italic>KIR3DS1<\/jats:italic> alleles. EBV loads did not differ by the <jats:italic>KIR3DL1<\/jats:italic> genotypes nor were they different between eBL survivors and non-survivors. Our results suggest that eBL pathogenesis may not simply involve variations in <jats:italic>KIR3DL1<\/jats:italic> and <jats:italic>KIR3DS1<\/jats:italic> genotypes. However, considering the complexity of the <jats:italic>KIR3DL1<\/jats:italic> locus, this study could not exclude a role for copy number variation in eBL pathogenesis.<\/jats:p>","DOI":"10.1371\/journal.pone.0275046","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T17:29:30Z","timestamp":1693416570000},"page":"e0275046","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of KIR3DL1\/KIR3DS1 allelic polymorphisms in Kenyan children with endemic Burkitt lymphoma"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9824-8706","authenticated-orcid":true,"given":"Beatrice M.","family":"Muriuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine S.","family":"Forconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erastus K.","family":"Kirwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titus K.","family":"Maina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonface O.","family":"Ariera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-1249","authenticated-orcid":true,"given":"Anita","family":"Ghansah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Moormann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3928-6774","authenticated-orcid":true,"given":"John M.","family":"Ong\u2019echa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"issue":"1","key":"pone.0275046.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ijc.2910060102","article-title":"Burkitt\u2019s lymphoma and malaria","volume":"6","author":"GW Kafuko","year":"1970","journal-title":"International Journal of Cancer"},{"issue":"993","key":"pone.0275046.ref002","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1136\/jcp.2007.047977","article-title":"Epstein\u2013Barr virus and Burkitt lymphoma","volume":"84","author":"G Brady","year":"2008","journal-title":"Postgraduate medical journal"},{"issue":"2","key":"pone.0275046.ref003","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1097\/00043426-199122000-00019","article-title":"African Burkitt\u2019s lymphoma: history, biology, clinical features, and treatment","volume":"13","author":"IT Magrath","year":"1991","journal-title":"Journal of Pediatric Hematology\/Oncology"},{"issue":"1","key":"pone.0275046.ref004","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ijc.22179","article-title":"Spatial clustering of endemic Burkitt\u2019s lymphoma in high\u2010risk regions of Kenya","volume":"120","author":"JJ Rainey","year":"2007","journal-title":"International journal of cancer"},{"issue":"5","key":"pone.0275046.ref005","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1158\/1541-7786.MCR-16-0305","article-title":"Comprehensive transcriptome and mutational profiling of endemic Burkitt lymphoma reveals EBV type\u2013specific differences","volume":"15","author":"Y Kaymaz","year":"2017","journal-title":"Molecular Cancer Research"},{"issue":"6","key":"pone.0275046.ref006","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1093\/infdis\/jir872","article-title":"Early age at time of primary Epstein\u2013Barr Virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the Etiology of Endemic Burkitt Lymphoma","volume":"205","author":"E Piriou","year":"2012","journal-title":"Journal of Infectious Diseases"},{"issue":"1","key":"pone.0275046.ref007","first-page":"19","article-title":"Etiology of Burkitt\u2019s lymphoma\u2014an alternative hypothesis to a vectored virus","volume":"42","author":"D. 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