Galvani Alison P, Novembre John
Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT 06520, USA.
Microbes Infect. 2005 Feb;7(2):302-9. doi: 10.1016/j.micinf.2004.12.006. Epub 2005 Jan 8.
The CCR5 chemokine receptor is exploited by HIV-1 to gain entry into CD4+ T cells. A deletion mutation (Delta32) confers resistance against HIV by obliterating the expression of the receptor on the cell surface. Intriguingly, this allele is young in evolutionary time, yet it has reached relatively high frequencies in Europe. These properties indicate that the mutation has been under intense positive selection. HIV-1 has not exerted selection for long enough on the human population to drive the CCR5-Delta32 allele to current frequencies, fueling debate regarding the selective pressure responsible for rise of the allele. The allele exists at appreciable frequencies only in Europe, and within Europe, the frequency is higher in the north. Here we review the population genetics of the CCR5 locus, the debate over the historical selective pressure acting on CCR5-Delta32, the inferences that can potentially be drawn from the geographic distribution of CCR5-Delta32 and the role that other genetic polymorphisms play in conferring resistance against HIV. We also discuss parallel evolution that has occurred at the CCR5 locus of other primate species. Finally, we highlight the promise that therapies based on interfering with the CCR5 receptor could have in the treatment of HIV.
CCR5趋化因子受体被HIV-1利用来进入CD4+T细胞。一种缺失突变（Delta32）通过消除细胞表面受体的表达赋予对HIV的抗性。有趣的是，这个等位基因在进化时间上很年轻，但在欧洲已达到相对较高的频率。这些特性表明该突变一直处于强烈的正选择之下。HIV-1对人类群体施加选择的时间还不够长，不足以将CCR5-Delta32等位基因推向当前频率，这引发了关于导致该等位基因频率上升的选择压力的争论。该等位基因仅在欧洲以可观的频率存在，并且在欧洲内部，其频率在北部更高。在这里，我们回顾了CCR5基因座的群体遗传学、关于作用于CCR5-Delta32的历史选择压力的争论、从CCR5-Delta32的地理分布中可能得出的推论以及其他基因多态性在赋予对HIV抗性方面所起的作用。我们还讨论了在其他灵长类物种的CCR5基因座上发生的平行进化。最后，我们强调基于干扰CCR5受体的疗法在治疗HIV方面可能具有的前景。
