Specific interaction of CXCR4 with CD4 and CD8{alpha}: Functional analysis of the CD4/CXCR4 interaction in the context of HIV-1 envelope glycoprotein-mediated membrane fusion
- Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115 (United States) and Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MA 02115 (United States)
- Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115 (United States)
- Office of Technology Information Systems, Bioinformatics and Computational Biology Program, National Institutes of Allergy and Infectious Diseases, Bethesda, MD 20892 (United States)
We investigated possible interactions between HIV-1 receptor (CD4) and the main coreceptors CXCR4 and CCR5. We found that CD4 and CXCR4 coexpressed in 293T cells form a complex that can be immunoprecipitated with antibodies directed against the extracellular domain of either protein. Mutagenesis revealed that the CD4/CXCR4 interaction maps to two previously uncharacterized basic motifs in the cytoplasmic domain of CD4. HIV-1 envelope glycoprotein-mediated membrane fusion was found to be independent of the ability of CD4 and CXCR4 to interact, whether fusion was studied in a virus-cell or a cell-cell model. However, this interaction might explain the adaptation of HIV-1 to CXCR4 as an alternative to CCR5. We found that CXCR4 also interacts with the cytoplasmic domain of CD8{alpha} in a way that is similar to the CD4/CXCR4 interaction. The CD4/CXCR4 and CD8{alpha}/CXCR4 interactions may thus be involved in cellular signaling pathways shared by the CD4 and CD8{alpha} molecules.
- OSTI ID:
- 20850559
- Journal Information:
- Virology, Vol. 353, Issue 1; Other Information: DOI: 10.1016/j.virol.2006.05.027; PII: S0042-6822(06)00358-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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