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.

TY - JOUR

T1 - 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.

AU - Mårtensson, Ulrika

AU - Fenyö, Eva Maria

AU - Olde, Björn

AU - Owman, Christer

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Medical Microbiology (013250400), Molecular Neurobiology (0131000140), Drug Target Discovery (013212045)

PY - 2006

Y1 - 2006

N2 - 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 transfiected 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. (c) 2006 Elsevier Inc. All rights reserved.

AB - 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 transfiected 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. (c) 2006 Elsevier Inc. All rights reserved.

KW - hybrid receptor model

KW - SIV

KW - chemerin receptor

KW - G-protein coupled receptor

KW - HIV-2

KW - HIV-1

U2 - 10.1016/j.virol.2006.07.010

DO - 10.1016/j.virol.2006.07.010

M3 - Article

VL - 355

SP - 6

EP - 17

JO - Virology

JF - Virology

SN - 1096-0341

IS - Aug 9

ER -