{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T18:53:26Z","timestamp":1772909606416,"version":"3.50.1"},"reference-count":36,"publisher":"Proceedings of the National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,1,8]]},"abstract":"<jats:p>\n            To study HIV-1 escape from a coreceptor antagonist,\n the R5 primary isolate CC1\/85 was passaged in peripheral blood\n mononuclear cells with increasing concentrations of the CCR5-specific\n small molecule inhibitor, AD101. By 19 passages, an escape\n mutant emerged with a &gt;20,000-fold resistance to AD101. This virus was\n cross-resistant to a related inhibitor, SCH-C, and partially\n resistant to RANTES but still sensitive to CCR5-specific mAbs. The\n resistant phenotype was stable; the mutant virus retained AD101\n resistance during nine additional passages of culture in the absence of\n inhibitor. Replication of the escape mutant in peripheral blood\n mononuclear cells completely depended on CCR5 expression and did not\n occur in cells from CCR5-\u039432 homozygous individuals. The escape\n mutant was unable to use CXCR4 or any other tested coreceptor to enter\n transfected cells. Acquisition of CXCR4 use is not the dominant\n            <jats:italic>in vitro<\/jats:italic>\n            escape pathway for a small molecule CCR5 entry\n inhibitor. Instead, HIV-1 acquires the ability to use CCR5 despite the\n inhibitor, first by requiring lower levels of CCR5 for entry and then\n probably by using the drug-bound form of the receptor.\n          <\/jats:p>","DOI":"10.1073\/pnas.012519099","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:36:44Z","timestamp":1027694204000},"page":"395-400","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":257,"title":["HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use"],"prefix":"10.1073","volume":"99","author":[{"given":"Alexandra","family":"Trkola","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine,\r University Hospital Zurich, 8091 Zurich, Switzerland;\r Weill Medical College of Cornell University, New York,\r NY 10021; and Schering Plough Research Institute, 2015\r Galloping Hill Road, Kenilworth, NJ 07033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn E.","family":"Kuhmann","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine,\r University Hospital Zurich, 8091 Zurich, Switzerland;\r Weill Medical College of Cornell University, New York,\r NY 10021; and Schering Plough Research Institute, 2015\r Galloping Hill Road, Kenilworth, NJ 07033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie M.","family":"Strizki","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine,\r University Hospital Zurich, 8091 Zurich, Switzerland;\r Weill Medical College of Cornell University, New York,\r NY 10021; and Schering Plough Research Institute, 2015\r Galloping Hill Road, Kenilworth, NJ 07033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine,\r University Hospital Zurich, 8091 Zurich, Switzerland;\r Weill Medical College of Cornell University, New York,\r NY 10021; and Schering Plough Research Institute, 2015\r Galloping Hill Road, Kenilworth, NJ 07033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Ketas","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine,\r University Hospital Zurich, 8091 Zurich, Switzerland;\r Weill Medical College of Cornell University, New York,\r NY 10021; 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