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.

Abstract

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.

• Authors: Ulrika E A Mårtensson, Eva Maria Fenyö, Björn Olde, Christer Owman
• Journal: Virology (Virology) Vol. 355 Issue 1 Pg. 6-17 (Nov 10 2006) ISSN: 0042-6822 [Print] United States
• PMID: 16904155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CMKLR1 protein, human
• HIV Core Protein p24
• Receptors, Chemokine
• Receptors, HIV
• Recombinant Proteins

Topics

• Amino Acid Sequence
• CD4-Positive T-Lymphocytes (virology)
• Cell Line, Tumor
• Cell Membrane (chemistry)
• Flow Cytometry
• HIV Core Protein p24 (biosynthesis)
• HIV-1 (growth & development, metabolism)
• HIV-2 (growth & development, metabolism)
• Humans
• Microscopy, Confocal
• Molecular Sequence Data
• Protein Structure, Tertiary
• Receptors, Chemokine (chemistry, genetics, metabolism)
• Receptors, HIV (chemistry, genetics, metabolism)
• Recombinant Proteins (metabolism)
• Sequence Homology, Amino Acid
• Simian Immunodeficiency Virus (growth & development, metabolism)
• Transfection
• Virus Attachment