Broad usage spectrum of G protein-coupled receptors as coreceptors by primary isolates of HIV.
OBJECTIVE
HIV-1 can use various G protein-coupled receptors (GPCRs) in addition to CCR5 and CXCR4 as coreceptors; however, this type of HIV-1 infection has hardly been detected in vivo. The objective of this study was to elucidate the spectrum of GPCR usage by HIV-1 populations in vivo.


METHODS
CD4-expressing glioma cell line, NP-2/CD4, becomes highly susceptible to HIV-1 when the cells express GPCRs with coreceptor activities. This cell system was advantageous for detecting the inefficient use of GPCRs by HIV-1.


METHODS
We developed NP-2/CD4/GPCR cells that express each of 23 GPCRs: 21 chemokine receptors (CCR1, CCR2b, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9B, CCR10, CCR11, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CX3CR1, XCR1, D6, and DARC) and two other GPCRs (a formylpeptide receptor, FPRL1, and an orphan GPCR, GPR1). NP-2/CD4/GPCR cells were directly cocultured with HIV-1-positive peripheral blood lymphocytes and HIV-1 infection was detected.


RESULTS
Primary HIV-1 isolates were obtained from NP-2/CD4/GPCR cells expressing CCR5, CXCR4, FPRL1, or GPR1 cocultured with 11 of 17 peripheral blood lymphocytes. Surprisingly, these isolates showed extremely expanded GPCR usage, such as CCR1, CCR3, CCR5, CCR8, CXCR4, D6, FPRL1, and GPR1 as coreceptors. We found that CCR9B, CCR10, and XCR1 also work as novel HIV-1 coreceptors.


CONCLUSIONS
FPRL1 and GPR1 have the potential to work as significant HIV-1 coreceptors in vivo next to CCR5 and CXCR4. HIV-1 populations that can use various GPCRs as coreceptors are already circulating in vivo, even in the early stage of HIV-1 infection.
Shimizu
Nobuaki
N
Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. gardy@med.gunma-u.ac.jp
Tanaka
Atsushi
A
Oue
Atsushi
A
Mori
Takahisa
T
Ohtsuki
Takahiro
T
Apichartpiyakul
Chatchawann
C
Uchiumi
Hideki
H
Nojima
Yoshihisa
Y
Hoshino
Hiroo
H
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor / Q000276:immunology; D002478:Cells, Cultured; D018450:Disease Progression; D014644:Genetic Variation / Q000235:genetics; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D010641:Phenotype; D054388:Receptors, CCR / Q000235:genetics* / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
D054388:Receptors, CCR; D054387:Receptors, CXCR; D043562:Receptors, G-Protein-Coupled