A Putative G Protein-Coupled Receptor, RDC1, Is a Novel Coreceptor for Human and Simian Immunodeficiency Viruses

doi:10.1128/JVI.74.2.619-626.2000

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Journal of Virology, January 2000, p. 619-626, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Putative G Protein-Coupled Receptor, RDC1, Is a Novel Coreceptor for Human and Simian Immunodeficiency Viruses

Nobuaki Shimizu,¹ Yasushi Soda,¹^,² Katsuaki Kanbe,¹ Hui-yu Liu,¹ Ryozaburo Mukai,³ Toshio Kitamura,⁴ and Hiroo Hoshino¹^,^*

Department of Virology and Preventive Medicine, Gunma University School of Medicine, Maebashi, Gunma 371-8511,¹ Japanese Foundation for AIDS Prevention, Minato-ku, Tokyo 108-1111,² Tukuba Primate Center for Medical Science, National Institute of Health, Japan, Tukuba, Ibaragi 305-0843,³ and Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 105-0071,⁴ Japan

Received 21 December 1998/Accepted 5 October 1999

More than 10 G protein-coupled receptors (GPCRs) have been shown to act as coreceptors for infection of human immunodeficiencyvirus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus(SIV). We have isolated HIV-1 variants infectious to primary brain-derivedCD4-positive cells (BT-3 and BT-20/N) and U87/CD4 glioma cellsthat are resistant to T-cell line-tropic (T-tropic), macrophage-tropic(M-tropic), and T- and M-tropic (dualtropic) (X4, R5, and R5X4)HIV-1 strains. These primary brain-derived cells were also highlysusceptible to HIV-2_ROD, HIV-2_SBL6669, and SIV_mndGB-1. A factoror coreceptor that determines the susceptibility of these brain-derivedcells to these HIV and SIV strains has not been fully identified.To identify this coreceptor, we examined amino acid sequencesof all known HIV and SIV coreceptors and noticed that tyrosineresidues are well conserved in their extracellular amino-terminaldomains. By this criterion, we selected 18 GPCRs as candidatesof coreceptors for HIV and SIV strains infectious to these brain-derivedcells. mRNA expression of an orphan GPCR, RDC1, was detected inthe brain-derived cells, the C8166 T-cell line, and peripheralblood lymphocytes, all of which are susceptible to HIV-1 variants,but not in macrophages, which are resistant to them. When a CD4-expressingcell line, NP-2/CD4, which shows strict resistance to infectionnot only with HIV-1 but also with HIV-2 or SIV, was transducedwith the RDC1 gene, the cells became highly susceptible to HIV-2and SIV_mnd strains but to neither M- nor T-tropic HIV-1 strains.The cells also acquired a low susceptibility to the HIV-1 variants.These findings indicate that RDC1 is a novel coreceptor for severalHIV-1, HIV-2, and SIV strains which infect brain-derivedcells.

^* Corresponding author. Mailing address: Department of Virology and Preventive Medicine, Gunma University School of Medicine,3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Phone: 81-27-220-8000.Fax: 81-27-220-8006. E-mail: hoshino{at}akagi.sb.gunma-u.ac.jp.

Journal of Virology, January 2000, p. 619-626, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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