The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/405/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 3, August 4, 1997 405-411

Articles

Two Orphan Seven-Transmembrane Segment Receptors Which Are Expressed in CD4-positive Cells Support Simian Immunodeficiency Virus Infection

Michael Farzan*, Hyeryun Choe*, Kathleen Martin§, Luisa Marcon*,||, Wolfgang Hofmann*, Gunilla Karlsson*, Ying Sun*, Peter Barrett§, Nathalie Marchand*, Nancy Sullivan*, Norma Gerard§, Craig Gerard§, and Joseph Sodroski*,{ddagger}

From the * Division of Human Retrovirology, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115; {ddagger} Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115; § Perlmutter Laboratory, Children's Hospital, and Department of Medicine and Department of Pediatrics, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02115; and || Institute of Microbiology, University of Padua Medical School, Padua, Italy 35121

Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4+ T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.

Address correspondence to Dr. Joseph Sodroski, JFB 824, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. Phone: 617-632-3371; FAX: 617-632-4338; E-mail: Joseph_Sodroski{at}DFCI.Harvard.edu or Dr. Craig Gerard, Perlmutter Laboratory, Children's Hospital, Hunnewell, 300 Longwood Avenue, Boston, MA 02115. Phone: 617-735-6174; FAX: 617-730-0422; E-mail: gerard_c{at}a1.tch.harvard.edu

1 Abbreviations used in this paper: 7-TMS, seven-transmembrane segment; CAT, chloramphenicol acetyltransferase; SIV, simian immunodeficiency virus.

M. Farzan and H. Choe contributed equally to this work.


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