{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:48:22Z","timestamp":1791920902913,"version":"4.3.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010753","name":"National Health Laboratory Service","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010753","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001338","name":"University of Capetown","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>HIV-1 infection often leads to the development of co-morbidities including cancer. Burkitt lymphoma (BL) is one of the most over-represented non-Hodgkin lymphoma among HIV-infected individuals, and displays a highly aggressive phenotype in this population group, with comparatively poorer outcomes, despite these patients being on anti-retroviral therapy. Accumulating evidence indicates that the molecular pathogenesis of HIV-associated malignancies is unique, with components of the virus playing an active role in driving oncogenesis, and in order to improve patient prognosis and treatment, a better understanding of disease pathobiology and progression is needed. In this study, we found HIV-1 Tat to be localized within the tumor cells of BL patients, and enhanced expression of oncogenic c-MYC in these cells. Using luciferase reporter assays we show that HIV-1 Tat enhances the<jats:italic>c-MYC<\/jats:italic>gene promoter activity and that this is partially mediated via two AP-1 binding elements located at positions -1128 and -1375 bp, as revealed by mutagenesis experiments. We further demonstrate, using pull-down assays, that Tat can exist within a protein complex with the AP-1 factor JunB, and that this complex can bind these AP-1 sites within the<jats:italic>c-MYC<\/jats:italic>promoter, as shown by<jats:italic>in vivo<\/jats:italic>chromatin immunoprecipitation assays. Therefore, these findings show that in HIV-infected individuals, Tat infiltrates B-cells, where it can enhance the expression of oncogenic factors, which contributes toward the more aggressive disease phenotype observed in these patients.<\/jats:p>","DOI":"10.3389\/fcell.2021.693706","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T05:44:24Z","timestamp":1625031864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["HIV-1 Transactivator of Transcription (Tat) Co-operates With AP-1 Factors to Enhance c-MYC Transcription"],"prefix":"10.3389","volume":"9","author":[{"given":"Leonardo","family":"Alves de Souza Rios","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lungile","family":"Mapekula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nontlantla","family":"Mdletshe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharshnee","family":"Chetty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaheen","family":"Mowla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.transci.2011.01.007","article-title":"Impact of the HIV epidemic and anti-retroviral treatment policy on lymphoma incidence and subtypes seen in the western cape of South Africa, 2002\u20132009: preliminary findings of the tygerberg lymphoma study group.","volume":"44","author":"Abayomi","year":"2011","journal-title":"Transfus. 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