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U.S.A."],"published-print":{"date-parts":[[2024,3,19]]},"abstract":"<jats:p>\n                    The discovery of the 32-bp deletion allele of the chemokine receptor gene\n                    <jats:italic>CCR5<\/jats:italic>\n                    showed that homozygous carriers display near-complete resistance to HIV infection, irrespective of exposure. Algorithms of molecular evolutionary theory suggested that the\n                    <jats:italic>\n                      CCR5-\n                      <jats:bold>\u2206<\/jats:bold>\n                      32\n                    <\/jats:italic>\n                    mutation occurred but once in the last millennium and rose by strong selective pressure relatively recently to a ~10% allele frequency in Europeans. Several lines of evidence support the hypothesis that\n                    <jats:italic>\n                      CCR5-\n                      <jats:bold>\u2206<\/jats:bold>\n                      32\n                    <\/jats:italic>\n                    was selected due to its protective influence to resist\n                    <jats:italic>Yersinia pestis,<\/jats:italic>\n                    the agent of the Black Death\/bubonic plague of the 14th century. Powerful anti-AIDS entry inhibitors targeting CCR5 were developed as a treatment for HIV patients, particularly those whose systems had developed resistance to powerful anti-retroviral therapies. Homozygous\n                    <jats:italic>\n                      CCR5-\n                      <jats:bold>\u2206<\/jats:bold>\n                      32\/\n                      <jats:bold>\u2206<\/jats:bold>\n                      32\n                    <\/jats:italic>\n                    stem cell transplant donors were used to produce HIV-cleared AIDS patients in at least five \u201ccures\u201d of HIV infection. CCR5 has also been implicated in regulating infection with\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , in recovery from stroke, and in ablation of the fatal graft versus host disease (GVHD) in cancer transplant patients. While homozygous\n                    <jats:italic>\n                      CCR5-\n                      <jats:bold>\u2206<\/jats:bold>\n                      32\/32\n                    <\/jats:italic>\n                    carriers block HIV infection, alternatively they display an increased risk for encephalomyelitis and death when infected with the West Nile virus.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2321907121","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T13:54:38Z","timestamp":1709906078000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["Legacy of a magic gene\u2014\n                    <i>\n                      CCR5-\n                      <b>\u2206<\/b>\n                      32\n                    <\/i>\n                    : From discovery to clinical benefit in a generation"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-0757","authenticated-orcid":false,"given":"Stephen J.","family":"OBrien","sequence":"first","affiliation":[{"name":"Guy Harvey Oceanographic Center, Halmos College of Arts and Sciences, Nova Southeastern University, Ft Lauderdale, FL 33004"},{"name":"Indiana University School of Public Health, Bloomington, IN 47405"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"e_1_3_5_1_2","first-page":"250","article-title":"Pneumocystis pneumonia\u2014Los Angeles","volume":"30","author":"Centers for Disease Control (CDC)","year":"1981","unstructured":"Centers for Disease Control (CDC), Pneumocystis pneumonia\u2014Los Angeles. 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