Carrington M, Dean M, Martin M P, O'Brien S J
Intramural Research Support Program, SAIC-Frederick, MD 21702-1201, USA.
Hum Mol Genet. 1999;8(10):1939-45. doi: 10.1093/hmg/8.10.1939.
The chemokine receptor gene, CCR5, has become a central theme in studies of host genetic effects on HIV-1 pathogenesis ever since the discovery that the CCR5 molecule serves as a major cell surface co-receptor for the virus. A growing number of genetic variants within the coding and 5' regulatory region of CCR5 have been identified, several of which have functional consequences for HIV-1 pathogenesis. Here we review the CCR5 literature describing CCR5 polymorphism and the functional ramifications that several of these variants have on HIV-1 infection and progression to AIDS. The multiplicity of CCR5 genetic effects on HIV-1 disease underscores the critical importance of this gene in controlling AIDS pathogenesis and provides the logic for develop-ment of therapeutic strategies that target the interaction of HIV-1 envelope and CCR5 in HIV-1 associated disease.
自从发现CCR5分子作为该病毒的主要细胞表面共受体以来,趋化因子受体基因CCR5已成为宿主基因对HIV-1发病机制影响研究的核心主题。在CCR5的编码区和5'调控区内,已鉴定出越来越多的基因变异,其中一些变异对HIV-1发病机制具有功能性影响。在此,我们综述了描述CCR5多态性以及其中几种变异对HIV-1感染和向艾滋病进展的功能影响的相关文献。CCR5基因对HIV-1疾病影响的多样性突出了该基因在控制艾滋病发病机制中的关键重要性,并为开发针对HIV-1相关疾病中HIV-1包膜与CCR5相互作用的治疗策略提供了理论依据。