biostudies-literatureUnknown111(19)Martinez-Munoz LCCR5 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 gp120IIIB 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(+) T cells, CCR5 expression led to a reduction in X4 HIV-1 infectivity. These findings can helProceedings of the National Academy of Sciences of the United States of AmericaE1960-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC4024905biostudies-literatureCCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.PMC4024905Rodriguez Frade JMBarroso RVega BFranco RDyrhaug SYSantiago CCostas CSoriano SFNavarro GMartinez-Munoz LMunoz-Fernandez MALucas PMellado MfalseCCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.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 gp120IIIB 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(+) T cells, CCR5 expression led to a reduction in X4 HIV-1 infectivity. These findings can hel2014-01-01T00:00:00Z2014 May2025-04-05T13:37:09.638Z2019-03-27T01:28:26ZS-EPMC40249052477823410.1073/pnas.1322887111