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...

We have characterized the structural and molecular interactions of CC-chemokine receptor 5 (CCR5) with three CCR5 inhibitors active against R5 human immunodeficiency virus type 1 (HIV-1) including the potent in vitro and in vivo CCR5 inhibitor aplaviroc (AVC). The data obtained with saturation binding assays and structural analyses delineated the key interactions responsible for the binding of ...

conclusions snps within the ccr5 gene should be considered as an important factor used in combination with other host gene snps when developing a mathematical model for anticipating response to hcv therapy. background chronic hepatitis c virus (hcv) infection is a globally serious public health issue. objectives in this study, we investigated cc chemokine receptor 5 (ccr5-59029) polymorphism wh...

Because the chemokine receptor CCR5 is expressed on Th1 CD4(+) cells, it is important to investigate the expression and function of this receptor on other T cells involved in Th1 immune responses, such as Ag-specific CD8(+) T cells, which to date have been only partially characterized. Therefore, we analyzed the expression and function of CCR5 on virus-specific CD8+ T cells identified by HLA cl...

The envelope glycoprotein (Env) of human immunodeficiency virus is key to viral entry of susceptible target cells and is therefore a major target for the design of vaccines and antiviral drugs. C-C chemokine receptor type 5 (CCR5)-using (R5) Env is the predominant phenotype associated with early transmission and acute infection. This study investigated the mechanism of CCR5 use and the sensitiv...

Previously, we have shown that CCR5 transcription is regulated by CREB-1. However, the ubiquitous pattern of CREB-1 expression suggests the involvement of an additional level of transcriptional control in the cell type-specific expression of CCR5. In this study, we show that epigenetic changes (i.e. DNA methylation and histone modifications) within the context of the CCR5 P1 promoter region cor...

Exposure to HIV does not necessarily result in infection. Because primary HIV infection is associated with CCR5-tropic HIV variants (R5), CCR5-specific Abs in the sera of HIV-seronegative, HIV-exposed individuals (ESN) might be associated with protection against infection. We analyzed sera from ESN, their HIV-infected sexual partners (HIV+), and healthy controls (USN) searching for CCR5-specifi...

We explore the impact of a host genetic factor on heterosexual HIV epidemics by using a deterministic mathematical model. A protective allele unequally distributed across populations is exemplified in our models by the 32-bp deletion in the host-cell chemokine receptor CCR5, CCR5!32. Individuals homozygous for CCR5!32 are protected against HIV infection whereas those heterozygous for CCR5!32 ha...