The CC chemokine I-309 inhibits CCR8-dependent infection by diverse HIV-1 strains.

Abstract

Using a chemokine receptor model based on known receptor sequences, we identified several members of the seven transmembrane domain G-protein superfamily as potential chemokine receptors. The orphan receptor ChemR1, which has recently been shown to be a receptor for the CC chemokine I-309, scored very high in our model. We have confirmed that I-309, but not a number of other chemokines, can induce a transient Ca2+ flux in cells expressing CCR8. In addition, the human erythroleukemic cell line K562 responded chemotactically in a dose-responsive manner to this chemokine. Since several chemokine receptors have been shown to be required as coreceptors for HIV-1 infection, we asked whether human immunodeficiency virus type 1 (HIV-1) could efficiently utilize CCR8. Here we show that the CCR8 receptor can serve as a coreceptor for diverse T-cell tropic, dual-tropic, and macrophage-tropic HIV-1 strains and that I-309 was a potent inhibitor of HIV-1 envelope-mediated cell-cell fusion and virus infection. Furthermore, we show by flow cytometry and immunohistochemistry that antibodies generated against the CCR8 receptor amino-terminal peptide cross-reacted with U-87 MG cells stably expressing CCR8, THP-1 cells, HL-60 cells, and human monocytes, a target cell for HIV-1 infectivity in vivo.

• Authors: R Horuk, J Hesselgesser, Y Zhou, D Faulds, M Halks-Miller, S Harvey, D Taub, M Samson, M Parmentier, J Rucker, B J Doranz, R W Doms
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 273 Issue 1 Pg. 386-91 (Jan 02 1998) ISSN: 0021-9258 [Print] United States
• PMID: 9417093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CCL1 protein, human
• CCR8 protein, human
• Chemokine CCL1
• Chemokines, CC
• Chemotactic Factors
• DNA, Complementary
• Receptors, CCR8
• Receptors, Chemokine
• Receptors, HIV

Topics

• Amino Acid Sequence
• Cell Line
• Chemokine CCL1
• Chemokines, CC
• Chemotactic Factors (chemistry, genetics, metabolism)
• DNA, Complementary
• HIV-1 (classification, pathogenicity)
• Humans
• Immunohistochemistry
• Molecular Sequence Data
• Receptors, CCR8
• Receptors, Chemokine (genetics, metabolism)
• Receptors, HIV (chemistry, metabolism)
• Sequence Homology, Amino Acid
• Species Specificity