CHEMR23, A PUTATIVE CHEMOATTRACTANT RECEPTOR, IS EXPRESSED IN MONOCYTE-DERIVED DENDRITIC CELLS AND MACROPHAGES AND IS A CORECEPTOR FOR SIV AND SOME PRIMARY HIV-1 STRAINS

Leukocyte chemoattractants act through a rapidly growing subfamily of G protein-coupled receptors. We report the cloning of a novel human ge ne encoding an orphan receptor (ChemR23) related to the C3a, C5a and f ormyl Met-Leu-Phe receptors, and more distantly to the subfamilies of chemokine receptors. ChemR23 transcripts were found to be abundant in monocyte-derived dendritic cells and macrophages, treated or not with LPS. Low expression could also be detected by reverse transcription-PC R in CD4(+) T lymphocytes. The gene encoding ChemR23 was assigned by r adiation hybrid mapping to the q21.2-21.3 region of human chromosome 1 2, outside the gene clusters identified so far for chemoattractant rec eptors. Given the increasing number of chemoattractant receptors used by HIV-I, HIV-2 and SIV as coreceptors, ChemR23 was tested in fusion a ssays for potential coreceptor activity by a range of viral strains. N one of the tested HIV-2 strains made use of ChemR23 as a coreceptor, b ut several SIV strains (SIVmac316, SIVmac239, SIVmac17E-Fr and SIVsm62 A), as well as a primary HIV-1 strain (92UG024-2) used it efficiently. ChemR23 therefore appears as a coreceptor for immunodeficiency viruse s that does not belong to the chemokine receptor family. It is also a putative chemoattractant receptor relatively specific for antigen-pres enting cells, and it could play an important role in the recruitment o r trafficking of these cell populations. Future work will be required to identify the ligand(s) of this new G protein-coupled receptor and t o define its precise role in the physiology of dendritic cells and mac rophages.