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CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 5/13/2014, Vol. 111 Issue 19, pE1960-E1969, 10p
- Publication Year :
- 2014
-
Abstract
- CCR5 and CXCR4, the respective cell surface coreceptors of R5 and X4 HIV-1 strains, both form heterodimers with CD4, the principal HIV-1 receptor. Using several resonance energy transfer techniques, we determined that CD4, CXCR4, and CCR5 formed heterotrimers, and that CCR5 coexpression altered the conformation of both CXCR4/CXCR4 homodimers and CD4/CXCR4 heterodimers. As a result, binding of the HIV-1 envelope protein gp120<subscript>IIIB</subscript> to the CD4/CXCR4/CCR5 heterooligomer was negligible, and the gp120- induced cytoskeletal rearrangements necessary for HIV-1 entry were prevented. CCR5 reduced HIV-1 envelope-induced CD4/ CXCR4-mediated cell-cell fusion. In nucleofected Jurkat CD4 cells and primary human CD4<superscript>+</superscript> T cells, CCR5 expression led to a reduction in X4 HIV-1 infectivity. These findings can help to understand why X4 HIV-1 strains infection affect T-cell types differently during AIDS development and indicate that receptor oligomerization might be a target for previously unidentified therapeutic approaches for AIDS intervention. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 111
- Issue :
- 19
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 96024945
- Full Text :
- https://doi.org/10.1073/pnas.1322887111