HIV-1 entry and macrophage inflammatory protein-1β-mediated signaling are independent functions of the chemokine receptor CCR5

Michael Farzan, Hyeryun Choe, Kathleen A. Martin, Ying Sun, Mary Sidelko, Charles R. Mackay, Norma P. Gerard, Joseph Sodroski, Craig Gerard

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Abstract

The human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter its target cell. The chemokine receptor CCR5 is used by macrophage-tropic strains of HIV-1, which predominate during the asymptomatic stages of infection. Here we investigate whether the ability of CCR5 to signal in response to its β-chemokine ligands is necessary or sufficient for viral entry. Three CCR5 mutants with little or no ability to mobilize calcium in response to macrophage inflammatory protein-1β could nonetheless support HIV-1 entry and the early steps in the virus life cycle with efficiencies comparable with those of wild-type CCR5. Conversely, a chimeric receptor with the N terminus of CCR2 replacing that of CCR5 responded to macrophage inflammatory protein-1β and MCP-1 but did not efficiently support viral entry. These results demonstrate that chemokine signaling and HIV-1 entry are separable functions of CCR5 and that only viral entry requires the N-terminal domain of CCR5.

Original languageEnglish
Pages (from-to)6854-6857
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number11
DOIs
Publication statusPublished - 14 Mar 1997
Externally publishedYes

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