Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection.
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.
Farzan
M
M
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Choe
H
H
Martin
K
K
Marcon
L
L
Hofmann
W
W
Karlsson
G
G
Sun
Y
Y
Barrett
P
P
Marchand
N
N
Sullivan
N
N
Gerard
N
N
Gerard
C
C
Sodroski
J
J
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D008253:Macaca mulatta; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000096:biosynthesis; D015728:Receptors, HIV / Q000096:biosynthesis; D011991:Receptors, Virus / Q000096:biosynthesis*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D011991:Receptors, Virus