Lin Yea-Lih, Mettling Clément, Portalès Pierre, Réant Brigitte, Clot Jacques, Corbeau Pierre
Laboratoire d'Immunologie, Hopital Saint Eloi, 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France.
J Virol. 2005 Jun;79(12):7938-41. doi: 10.1128/JVI.79.12.7938-7941.2005.
The binding of R5 envelope to CCR5 during human immunodeficiency virus type 1 (HIV-1) entry provokes cell activation, which has so far been considered to have no effect on virus replication, since signaling-defective CCR5 molecules have been shown to function normally as HIV-1 coreceptors on transformed cells or mitogen-stimulated T lymphocytes. As the background state of activation of these cells might have biased the results, we performed experiments using the same approach but with nonactivated primary T lymphocytes. We now report that the single R126N mutation in the DRY motif, involved in G-protein coupling, results in a signaling-defective CCR5 coreceptor with a drastically impaired capacity to support HIV-1 infection.
在人类免疫缺陷病毒1型（HIV-1）进入过程中，R5包膜与CCR5的结合会引发细胞活化，迄今为止，这一过程被认为对病毒复制没有影响，因为信号缺陷型CCR5分子已被证明在转化细胞或丝裂原刺激的T淋巴细胞上作为HIV-1共受体能正常发挥功能。由于这些细胞的活化背景状态可能使结果产生偏差，我们采用相同方法但使用未活化的原代T淋巴细胞进行了实验。我们现在报告，参与G蛋白偶联的DRY基序中的单个R126N突变会导致信号缺陷型CCR5共受体，其支持HIV-1感染的能力大幅受损。
