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 gene encoding an orphan receptor (ChemR23) related to the C3a, C5a and formyl 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-PCR in CD4+ T lymphocytes. The gene encoding ChemR23 was assigned by radiation hybrid mapping to the q21.2-21.3 region of human chromosome 12, outside the gene clusters identified so far for chemoattractant receptors. Given the increasing number of chemoattractant receptors used by HIV-1, HIV-2 and SIV as coreceptors, ChemR23 was tested in fusion assays for potential coreceptor activity by a range of viral strains. None of the tested HIV-2 strains made use of ChemR23 as a coreceptor, but several SIV strains (SIVmac316, SIVmac239, SIVmacl7E-Fr and SIVsm62A), as well as a primary HIV-1 strain (92UG024-2) used it efficiently. ChemR23 therefore appears as a coreceptor for immunodeficiency viruses that does not belong to the chemokine receptor family. It is also a putative chemoattractant receptor relatively specific for antigen-presenting cells, and it could play an important role in the recruitment or trafficking of these cell populations. Future work will be required to identify the ligand(s) of this new G protein-coupled receptor and to define its precise role in the physiology of dendritic cells and macrophages.
Samson
M
M
IRIBHN, Université libre de Bruxelles, Belgium.
Edinger
A L
AL
Stordeur
P
P
Rucker
J
J
Verhasselt
V
V
Sharron
M
M
Govaerts
C
C
Mollereau
C
C
Vassart
G
G
Doms
R W
RW
Parmentier
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D001483:Base Sequence; D002460:Cell Line; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011951:Receptors, Complement / Q000737:chemistry; D044042:Receptors, Formyl Peptide; D015728:Receptors, HIV / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry; D018000:Receptors, Peptide / Q000737:chemistry; D011991:Receptors, Virus / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C102741:CMKLR1 protein, human; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D011951:Receptors, Complement; D044042:Receptors, Formyl Peptide; D015728:Receptors, HIV; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D011991:Receptors, Virus