Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5(+/+), T cells from CCR5(-/-) mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-Delta32/Delta32 homozygotes) as well as after Ab-me...

BACKGROUND This study aimed to examine how CC chemokine receptor 5 (CCR5) inhibitors (aplaviroc [APL], TAK779 and maraviroc [MVC]) interact with CCR5 and affect its dynamics and physiological CC-chemokine-CCR5 interactions. METHODS A yellow fluorescent protein (YFP)-tagged CCR5-expressing U373-MAGI cell line was generated and a stable CCR5-expressing clonal population, (YFP)CCR5-UM16, was pre...

We have shown that mice that express the C-C chemokine receptor 5 (CCR5) have enhanced local tumor growth and an impaired response to vaccine therapy compared with CCR5 knockout (CCR5(-/-)) mice. Here, we extend these observations to evaluate the function of CCR5 in pulmonary metastasis and the mechanism underlying the diminished tumor growth in CCR5(-/-) mice. Lung metastases were counted in w...

The requirement of human immunodeficiency virus (HIV)-induced CCR5 activation for infection by R5 HIV type 1 (HIV-1) strains remains controversial. Ectopic CCR5 expression in CD4(+)-transformed cells or pharmacological inhibition of G(alpha)i proteins coupled to CCR5 left unsolved whether CCR5-dependent cell activation is necessary for the HIV life cycle. In this study, we investigated the role...

HIV-1 strains that use CCR5 predominate after transmission and during the asymptomatic period of disease. However, in up to half of infected people, variants that use CXCR4 emerge, coincident with accelerated disease progression. The earliest CXCR4 using strains to appear, called R5X4 viruses, usually retain CCR5 use. Prototype R5X4 HIV-1 isolates infect macrophages using CCR5 and CXCR4, but CD...

A panel of four CCR5 monoclonal antibodies (mAbs) recognizing different epitopes on CCR5 was examined in CCR5-mediated cell-cell fusion assay, alone or in combination with a variety of small molecule CCR5 antagonists. Although no antagonism was observed between any of the CCR5 inhibitors, surprisingly potent synergy was observed between CCR5 mAbs and antagonists, and the synergistic activity wa...

HIV-1 strains that use CCR5 predominate after transmission and during the asymptomatic period of disease. However, in up to half of infected people, variants that use CXCR4 emerge, coincident with accelerated disease progression. The earliest CXCR4 using strains to appear, called R5X4 viruses, usually retain CCR5 use. Prototype R5X4 HIV-1 isolates infect macrophages using CCR5 and CXCR4, but CD...