CCR5 Levels and Expression Pattern Correlate with Infectability by Macrophage-tropic HIV-1, In Vitro
Lijun Wu,William A. Paxton,Nasim Kassam,Nancy Ruffing,James B. Rottman,Nancy Sullivan,Hyeryun Choe,Joseph Sodroski,Walter Newman,Richard A. Koup,Charles R. Mackay +10 more
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Anti-CCR5 mAbs were poor inhibitors of chemokine binding, indicating that HIV-1 and ligands bind to separate, but overlapping regions of CCR5, and demonstrate the feasibility of blocking macrophage-tropic HIV- 1 entry into cells with an anti-CCr5 reagent.Abstract:
Chemokine receptors serve as coreceptors for HIV entry into CD4+ cells. Their expression is thought to determine the tropism of viral strains for different cell types, and also to influence susceptibility to infection and rates of disease progression. Of the chemokine receptors, CCR5 is the most important for viral transmission, since CCR5 is the principal receptor for primary, macrophage-tropic viruses, and individuals homozygous for a defective CCR5 allele (Δ32/ Δ32) are highly resistant to infection with HIV-1. In this study, CCR5-specific mAbs were generated using transfectants expressing high levels of CCR5. The specificity of these mAbs was confirmed using a broad panel of chemokine receptor transfectants, and by their non-reactivity with T cells from Δ32/Δ32 individuals. CCR5 showed a distinct pattern of expression, being abundant on long-term activated, IL-2–stimulated T cells, on a subset of effector/memory T cells in blood, and on tissue macrophages. A comparison of normal and CCR5 Δ32 heterozygotes revealed markedly reduced expression of CCR5 on T cells from the heterozygotes. There was considerable individual to individual variability in the expression of CCR5 on blood T cells, that related to factors other than CCR5 genotype. Low expression of CCR5 correlated with the reduced infectability of T cells with macrophage-tropic HIV-1, in vitro. Anti-CCR5 mAbs inhibited the infection of PBMC by macrophage-tropic HIV-1 in vitro, but did not inhibit infection by T cell–tropic virus. Anti-CCR5 mAbs were poor inhibitors of chemokine binding, indicating that HIV-1 and ligands bind to separate, but overlapping regions of CCR5. These results illustrate many of the important biological features of CCR5, and demonstrate the feasibility of blocking macrophage-tropic HIV-1 entry into cells with an anti-CCR5 reagent.read more
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Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
TL;DR: It is shown that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets, which are named central memory (TCM) and effector memory (TEM).
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CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and Disease
TL;DR: In this paper, the chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophagetropic HIV-1 isolates, respectively.
Journal ArticleDOI
The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.
Shixin Qin,James B. Rottman,Paul Myers,Nasim Kassam,Michael E. Weinblatt,Marcel Loetscher,Alisa E. Koch,Bernhard Moser,Charles R. Mackay +8 more
TL;DR: Results demonstrate that the chemokine receptor CXCR3 and CCR5 are markers for T cells associated with certain inflammatory reactions, particularly TH-1 type reactions, and appear to identify subsets of T cells in blood with a predilection for homing to these sites.
Journal ArticleDOI
Effects of CCR5 and CD4 Cell Surface Concentrations on Infections by Macrophagetropic Isolates of Human Immunodeficiency Virus Type 1
TL;DR: It is concluded that CD4 and CCR5 directly or indirectly interact in a concentration-dependent manner within a pathway that is essential for infection by macrophagetropic HIV-1 and that the requirements for each are increased when the other component is present in a limiting amount.
Journal ArticleDOI
The Influence of CCL3L1 Gene-Containing Segmental Duplications on HIV-1/AIDS Susceptibility
Enrique Gonzalez,Hemant Kulkarni,Hector Bolivar,Andrea Mangano,Racquel Sanchez,Gabriel Catano,Robert J. B. Nibbs,Barry I. Freedman,Marlon P. Quinones,Michael J. Bamshad,Krishna K. Murthy,Brad H. Rovin,William E. Bradley,Robert A. Clark,Stephanie A. Anderson,Robert J. O'Connell,Brian K. Agan,Seema S. Ahuja,Rosa Bologna,Luisa Sen,Matthew J. Dolan,Sunil K. Ahuja +21 more
TL;DR: It is shown that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1, a potent human immunodeficiency virus–1 (HIV-1)–suppressive chemokine and ligand for the HIV coreceptor CCR5.
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