An orphan G protein-coupled receptor, GPR1, acts as a coreceptor to allow replication of human immunodeficiency virus types 1 and 2 in brain-derived cells.
Twelve G protein-coupled receptors, including chemokine receptors, act as coreceptors and determinants for the cell tropisms of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV). We isolated HIV-1 variants from T-cell-line (T)- and macrophage (M)-tropic (i.e., dualtropic) (R5-R3-X4) HIV-1 strains and also produced six HIV-1 mutants carrying single-point amino acid substitutions at the tip of the V3 region of the Env protein of HIV-1. These variants and three mutants infected brain-derived CD4-positive cells that are resistant to M-, T-, or dualtropic (R5, X4, or R5-X4) HIV-1 strains. However, a factor that determines this cell tropism has not been identified. This study shows that primary brain-derived fibroblast-like cell strains, BT-3 and BT-20/N, as well as a CD4-transduced glioma cell line, U87/CD4, which were susceptible to these HIV-1 variants and mutants and the HIV-2ROD strain, expressed mRNA of an orphan G protein-coupled receptor (GPCR), GPR1. When a CD4-positive cell line which was strictly resistant to infection with diverse HIV-1 and HIV-2 strains was transduced with GPR1, the cell line became susceptible to these HIV-1 variants and mutants and to an HIV-2 strain but not to T- or dualtropic HIV-1 strains, and numerous syncytia formed after infection. These results indicate that GPR1 functions as a coreceptor for the HIV-1 variants and mutants and for the HIV-2ROD strain in vitro.
Shimizu
N
N
Department of Hygiene and Virology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Minato-ku, Tokyo 105-0071, Japan.
Soda
Y
Y
Kanbe
K
K
Liu
H Y
HY
Jinno
A
A
Kitamura
T
T
Hoshino
H
H
D001921:Brain / Q000821:virology; D002460:Cell Line; D005910:Glioma / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D015728:Receptors, HIV / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship; D014779:Virus Replication
C109334:GPR1 protein, S cerevisiae; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015728:Receptors, HIV; D029701:Saccharomyces cerevisiae Proteins