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The amount of CD4 coimmunoprecipitated with CCR5 was significantly higher than that with the other major HIV coreceptor, CXCR4, and in contrast to CXCR4 the CD4\u2013CCR5 coimmunoprecipitation was not significantly increased by gp120. The CD4\u2013CCR5 interaction probably takes place via the second extracellular loop of CCR5 and the first two domains of CD4. It can be inhibited by CCR5- and CD4-specific antibodies that interfere with HIV-1 infection, indicating a possible role in virus entry. These findings suggest a possible pathway of HIV-1 evolution and development of immunopathogenicity, a potential new target for antiretroviral drugs and a tool for development of vaccines based on Env\u2013CD4\u2013CCR5 complexes. The constitutive association of a seven-transmembrane-domain G protein-coupled receptor with another receptor also indicates new possibilities for cross-talk between cell surface receptors.<\/jats:p>","DOI":"10.1073\/pnas.96.13.7496","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"7496-7501","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":147,"title":["Constitutive cell surface association between CD4 and CCR5"],"prefix":"10.1073","volume":"96","author":[{"given":"Xiaodong","family":"Xiao","sequence":"first","affiliation":[{"name":"Laboratory of Experimental and Computational Biology, National Cancer Institute\u2013Frederick Cancer Research and Development Center, National Institutes of Health, Miller Drive, Frederick, MD 21702-1201; LeukoSite, Inc., 215 First Street, Cambridge, MA 02142; Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799; Centre d\u2019Immunologie de Marseille-Luminy, 163 Avenue de Luminy, Case 906, 13288 Marseille Cedex 9,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental and Computational Biology, National Cancer Institute\u2013Frederick Cancer Research and Development Center, National Institutes of Health, Miller Drive, Frederick, MD 21702-1201; LeukoSite, Inc., 215 First Street, Cambridge, MA 02142; Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799; Centre d\u2019Immunologie de Marseille-Luminy, 163 Avenue de Luminy, Case 906, 13288 Marseille Cedex 9,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzanko S.","family":"Stantchev","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental and Computational Biology, National Cancer Institute\u2013Frederick Cancer Research and Development Center, National Institutes of Health, Miller Drive, Frederick, MD 21702-1201; 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