{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:13:14Z","timestamp":1790316794130,"version":"4.1.0"},"reference-count":70,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"12","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:p>\n                    CCR5 serves as R5-tropic HIV co-receptor. Knocking out CCR5 in HIV patients, which has occurred &lt;10 times, is believed important for cure. JAK\/STAT inhibitors tofacitinib and ruxolitinib inhibit CCR5 expression in HIV\n                    <jats:sup>+<\/jats:sup>\n                    viremic patients. We investigated the association of JAK\/STAT signaling pathway with CCR5\/CCR2 expression in human primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and confirmed its importance. Six of nine JAK\/STAT inhibitors that reduced CCR5\/CCR2 expression were identified. Inhibitor-treated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells were relatively resistant, specifically to R5-tropic HIV infection. Furthermore, single JAK2, STAT3, STAT5A, and STAT5B knockout and different combinations of JAK\/STAT knockout significantly reduced CCR2\/CCR5 expression of both RNA and protein levels, indicating that CCR5\/CCR2 expression was positively regulated by JAK-STAT pathway in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Serum and glucocorticoid-regulated kinase 1 (SGK1) knockout affected CCR2\/CCR5 gene expression, suggesting that SGK1 is involved in CCR2\/CCR5 regulation. If cell surface CCR5 levels can be specifically and markedly down-regulated without adverse effects, that may  have a major impact on the HIV cure agenda.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adl0368","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T13:59:03Z","timestamp":1710943143000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["JAK\/STAT signaling pathway affects CCR5 expression in human CD4\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5095-8784","authenticated-orcid":true,"given":"Lingyun","family":"Wang","sequence":"first","affiliation":[{"name":"Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunus","family":"Yukselten","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-2382","authenticated-orcid":true,"given":"Julius","family":"Nuwagaba","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7418-2378","authenticated-orcid":true,"given":"Richard E.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/381661a0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80110-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1097-1160"},{"key":"e_1_3_2_5_2","first-page":"181","article-title":"Association between the CCR2-Val64Ile polymorphism and susceptibility to HIV-1 infection: A meta-analysis","volume":"4","author":"Ding D.-L.","year":"2011","unstructured":"D.-L. 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