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To address this issue, a series of mechanisms are proposed, supported by evidence from different fields, by which CD38 overexpression can facilitate CD4 T cell depletion in HIV infection. According to this model, increased catalytic activity of CD38 may reduce CD4 T cells\u2019 cytoplasmic nicotin\u2010amide adenine dinucleotide (NAD), leading to a chronic Warburg effect. This will reduce mitochondrial function. Simultaneously, CD38's catalytic products ADPR and cADPR may be transported to the cytoplasm, where they can activate calcium channels and increase cytoplasmic Ca\n                      <jats:sup>2+<\/jats:sup>\n                      concentrations, further altering mitochondrial integrity. These mechanisms will decrease the viability and regenerative capacity of CD4 T cells. These hypotheses can be tested experimentally, and might reveal novel therapeutic targets. Also see the video abstract here\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/youtu.be\/k1LTyiTKPKs\">https:\/\/youtu.be\/k1LTyiTKPKs<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bies.201800128","type":"journal-article","created":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T07:36:31Z","timestamp":1544427391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["HIV Disease Progression: Overexpression of the Ectoenzyme CD38 as a Contributory Factor?"],"prefix":"10.1002","volume":"41","author":[{"given":"Juan C.","family":"Rodr\u00edguez\u2010Alba","sequence":"first","affiliation":[{"name":"Flow Cytometry Core Facility Instituto de Ciencias de la Salud Universidad Veracruzana Av. 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