Characterization of the human chemerin receptor--ChemR23/CMKLR1--as co-receptor for human and simian immunodeficiency virus infection, and identification of virus-binding receptor domains.
Studies were conducted to elucidate co-receptor spectrum and function of the inflammatory receptor, CMKLR1/ChemR23, which was recently identified as the receptor for the cystatin-like chemoattractant, TIG2, also named chemerin. An infection model was applied based on stably transfected NP-2.CD4 host cells expressing various co-receptor constructs and exposed to panels of HIV-1, HIV-2 and SIV primary isolates. In a panel of 27 HIV-1 isolates tested, 12 isolates could use CMKLR1/ChemR23. As expected from a relatively high sequence homology with the extracellular domains of CCR3, HIV-1 isolates showing R3 tropism were particularly efficient in using CMKLR1/ChemR23. In addition, 5 out of 7 HIV-2 isolates and 13 out of 15 SIV (SMM-3 origin) used CMKLR1/ChemR23, in accordance with the previously documented ability of these isolates to use several co-receptors. In order to define important extracellular epitopes for the viral interaction, a hybrid receptor model was applied. This was based on the fact that the rat receptor, although structurally very similar to the human orthologue, was inefficient as viral co-receptor. When the rat receptor was "humanized" to include regions unique to the human receptor (N-terminus or second extracellular loop), exposure to HIV-1, HIV-2 and SIV isolates resulted in infection. The relative importance of the two critical receptor regions differed between HIV-1/HIV-2 on the one hand and SIV on the other. The results strongly support that the chemerin receptor, in the presence of CD4, functions as a "minor co-receptor" promoting infection by these classes of viruses.
Mårtensson
Ulrika E A
UE
Division of Molecular Neurobiology, Wallenberg Neuroscience Center, Lund University, SE-223 62, Sweden. Ulrika.Martensson@med.lu.se
Fenyö
Eva Maria
EM
Olde
Björn
B
Owman
Christer
C
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development / Q000378:metabolism*; D015498:HIV-2 / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019707:Receptors, Chemokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000378:metabolism*; D014162:Transfection; D053585:Virus Attachment
C102741:CMKLR1 protein, human; D016655:HIV Core Protein p24; D019707:Receptors, Chemokine; D015728:Receptors, HIV; D011994:Recombinant Proteins