共 42 条
HIV-1 infection through the CCR5 receptor is blocked by receptor dimerization
被引:127
作者:
Vila-Coro, AJ
[1
]
Mellado, M
[1
]
de Ana, AM
[1
]
Lucas, P
[1
]
del Real, G
[1
]
Martinez, C
[1
]
Rodriguez-Frade, JM
[1
]
机构:
[1] Univ Autonoma Madrid, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28049 Madrid, Spain
来源:
关键词:
AIDS;
chemokine;
chemokine receptor;
D O I:
10.1073/pnas.050457797
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
The identification of the chemokine receptors as receptors for HIV-1 has boosted interest in these molecules, raising expectations for the development of new strategies to prevent HIV-1 infection. The discovery that chemokines block HIV-1 replication has focused attention on identifying their mechanism of action. Previous studies concluded that this inhibitory effect may be mediated by steric hindrance or by receptor down-regulation. We have identified a CCR5 receptor-specific mAb that neither competes with the chemokine for binding nor triggers signaling, as measured by Ca2+ influx or chemotaxis. The antibody neither triggers receptor down-regulation nor interferes with the R5 JRFL viral strain gp120 binding to CCR5, but blocks HIV-1 replication in both in vitro assays using peripheral blood mononuclear cells as HIV-1 targets, as well as in vivo using human peripheral blood mononuclear cell-reconstituted SCID (severe combined immunodeficient) mice. Our evidence shows that the anti-CCR5 mAb efficiently prevents HIV-1 infection by inducing receptor dimerization. Chemokine receptor dimerization also is induced by chemokines and is required for their anti-HIV-1 activity. In addition to providing a molecular mechanism through which chemokines black HIV-1 infection, these results illustrate the prospects for developing new tools that possess HIV-1 suppressor activity, but lack the undesired inflammatory side effects of the chemokines.
引用
收藏
页码:3388 / 3393
页数:6
相关论文