Farzan M, Choe H, Martin K, Marcon L, Hofmann W, Karlsson G, Sun Y, Barrett P, Marchand N, Sullivan N, Gerard N, Gerard C, Sodroski J
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
J Exp Med. 1997 Aug 4;186(3):405-11. doi: 10.1084/jem.186.3.405.
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.
灵长类免疫缺陷病毒的临床分离株，包括1型人类免疫缺陷病毒（HIV-1），通过依次与CD4和趋化因子受体CCR5（七跨膜受体家族的一员）结合进入靶细胞。使用其他趋化因子受体的HIV-1变体存在于中枢神经系统中或在感染过程中出现。猿猴免疫缺陷病毒（SIV）已被证明使用CCR5作为共受体，但尚未鉴定出这些病毒的其他受体。在此我们表明，两个孤儿七跨膜片段受体gpr1和gpr15作为SIV的共受体，并在人肺泡巨噬细胞中表达。其中效率更高的gpr15也在人CD4(+) T淋巴细胞和活化的恒河猴外周血单个核细胞中表达。gpr15和gpr1蛋白缺乏趋化因子受体的几个特征，但与CCR5共享富含酪氨酸残基的氨基末端基序。这些结果强调了用作灵长类免疫缺陷病毒进入辅助因子的七跨膜片段受体的潜在多样性，并可能有助于理解病毒变异和发病机制。
