Abstract
Several members of the chemokine-receptor family serve, in conjunction with CD4, as receptors for the entry of human immunodeficiency virus type I (HIV-1) into cells1,2,3,4,5,6. The principal receptor for entry of macrophage-tropic (M-tropic) HIV-1 strains is CCR5, whereas that for T-cell-line-tropic (T-tropic) strains is CXCR4. Unlike HIV-1, infection with either M-tropic or T-tropic strains of simian immunodeficiency virus (SIV) can be mediated by CCR5, but not CXCR4 (refs 7, 8, 9, 10). SIV strains will also infect CD4+ cells that lack CCR5, which suggests that these strains use as yet unidentified receptors7,9,10. Here we use an expression-cloning strategy to identify SIV receptors and have isolated genes encoding two members of the seven-transmembrane G-protein-coupled receptor family that are used not only by SIVs, but also by strains of HIV-2 and M-tropic HIV-1. Both receptors are closely related to the chemokine-receptor family and are expressed in lymphoid tissues. One of the receptors is also expressed in colon and may therefore be important in viral transmission. Usage of these new receptors following experimental infection of non-human primates with SIV strains may provide important insight into viral transmission and the mechanisms of SIV- and HIV-induced acquired immune-deficiency syndrome.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Feng, Y., Broder, C. C., Kennedy, P. E. & Berger, E. A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872–877 (1996).
Deng, H. et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381, 661–666 (1996).
Alkhatib, G. et al. CC CKR5: a RANTES, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272, 1955–1958 (1996).
Dragic, T. et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381, 667–673 (1996).
Doranz, B. J. et al. Adual-tropic primary HIV-1 isolate that uses fusin and the β-chemokine receptors CKR-5, CKR-3 and CKR-2b as fusion cofactors. Cell 85, 1149–1158 (1996).
Choe, H. et al. The beta-chemokine receptors CCR3 and CCR5 faciitate infection by primary HIV-1 isolates. Cell 85, 1135–1148 (1996).
Chen, Z., Zhou, P., Ho, D. D., Landau, N. R. & Marx, P. A. Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. J. Virol. 71, 2705–2715 (1997).
Marcon, L. et al. Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239. J. Virol. 71, 2522–2527 (1997).
Edinger, A. L. et al. Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains. Proc. Natl Acad. Sci. USA 94, 4005–4010 (1997).
Hill, C. M. et al. Envelope glycoproteins from HIV-1, HIV-2, and SIV can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor. J. Virol. (in the press).
Marthas, M. L. et al. Rhesus macaques inoculated with molecularly cloned simian immunodeficiency virus. J. Med. Primatol. 18, 311–319 (1989).
Fukasawa, M. et al. Sequence of simian immunodeficiency virus from African green monkey, a new member of the HIV/SIV group. Nature 333, 457–461 (1988).
Clapham, P. R., Blanc, D. & Weiss, R. A. Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by simian immunodeficiency virus. Virology 181, 703–715 (1991).
Stefano, K. A. et al. Replication of a macrophage-tropic strain of human immunodeficiency virus type 1 (HIV-1) in a hybrid cell line, CEM × 174, suggests that cellular accessory molecules are required for HIV-1 entry. J. Virol. 67, 6707–6715 (1993).
Heiber, M. et al. Anovel human gene encoding a G-protein-coupled receptor (GPR15) is located on chromosome 3. Genomics 32, 462–465 (1996).
He, J. et al. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature 385, 645–649 (1997).
Fauci, A. S. Host factors and the pathogenesis of HIV-induced disease. Nature 384, 529–534 (1996).
Desrosiers, R. C. The simian immunodeficiency viruses. Annu. Rev. Immunol. 8, 557–578 (1990).
Kestler, H. et al. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science 248, 1109–1112 (1990).
Theodorou, I., Meyer, L., Magierowska, M., Katlama, C. & Rouzioux, C. HIV-1 infection in an individual homozygous for CCR5 delta 32. Seroco Study Group. Lancet 349, 1219–1220 (1997).
Biti, R. et al. HIV-1 infection in an individual homozygous for the CCR5 deletion allele. Nature Med. 3, 252–253 (1997).
O'Brien, T. R. et al. HIV-1 infection in a man homozygous for CCR5 delta 32. Lancet 349, 1219 (1997).
Kitamura, T. et al. Efficient screening of retroviral cDNA expression libraries. Proc. Natl Acad. Sci. USA 92, 9146–9150 (1995).
Landau, N. R., Page, K. A. & Littman, D. R. Pseudotyping with human T-cell leukemia virus type I broadens the human immunodeficiency virus host range. J. Virol. 65, 162–169 (1991).
Westervelt, P., Gendelman, H. E. & Ratner, L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc. Natl Acad. Sci. USA 88, 3097–3101 (1991).
Hwang, S. S., Boyle, T. J., Lyerly, H. K. & Cullen, B. R. Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1. Science 257, 535–537 (1992).
Gao, F. et al. Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. (The WHO and NIAID Networks for HIV Isolation and Characterization.) J. Virol. 70, 1651–1657 (1996).
Barnett, S. W., Quiroga, M., Werner, A., Dina, D. & Levy, J. A. Distinguishing features of an infectious molecular clone of the highly divergent and noncytopathic human immunodeficiency virus type 2 UC1 strain. J. Virol. 67, 1006–1014 (1993).
Kong, L. I. et al. West African HIV-2-related human retrovirus with attenuated cytopathicity. Science 240, 1525–1529 (1988).
Gao, F. et al. Human infection by genetically diverse SIVSM-related HIV-2 in west Africa. Nature 358, 495–499 (1992).
Liao, S. et al. J. Exp. Med. 185, 2015–2023 (1997).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Deng, H., Unutmaz, D., KewalRamani, V. et al. Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 388, 296–300 (1997). https://doi.org/10.1038/40894
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/40894
This article is cited by
-
Timely T cell recruitment protects against viral myocarditis
Nature Cardiovascular Research (2023)
-
Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15
Nature Communications (2023)
-
Tobacco-smoking induced GPR15-expressing T cells in blood do not indicate pulmonary damage
BMC Pulmonary Medicine (2017)
-
G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
Scientific Reports (2017)
-
Comparison of immune responses to attenuated rabies virus and street virus in mouse brain
Archives of Virology (2017)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.