Chen Z, Kwon D, Jin Z, Monard S, Telfer P, Jones M S, Lu C Y, Aguilar R F, Ho D D, Marx P A
Aaron Diamond AIDS Research Center, The Rockefeller University, New York 10016, USA.
J Exp Med. 1998 Dec 7;188(11):2057-65. doi: 10.1084/jem.188.11.2057.
A homozygous 24-bp deletion (Delta24) was found in the CC chemokine receptor 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquatus torquatus, both in Africa and in an American zoo. The CCR5 Delta24 defect encompassed eight amino acids in frame in the fourth transmembrane region. Unexpectedly, RCM-009, one of 11 homozygotes (Delta24CCR5/ Delta24CCR5), was found to be naturally infected with a divergent simian immunodeficiency virus (SIV) strain, which was not R5-tropic, but used CCR2b (R2b) as its major coreceptor. SIVrcmGab1 was the only R2b-tropic SIV among other divergent SIVs tested. Cells transfected with the Delta24 CCR5 did not support entry of R5-tropic SIVmac, SIVcpz, SIVmne, HIV-2, or HIV-1, and were also inactive in signal transduction mediated by beta-chemokines. At 86.6%, the Delta24 allelic frequency was significantly higher than that of the 32-bp deletion found in humans. The Delta24 frequency was 4.1% in 34 sooty mangabeys (SMs), a geographically isolated subspecies that was naturally infected with R5-tropic SIV. Finding identical deletions in two mangabey subspecies separated for 10,000 years or more dates the Delta24 CCR5 deletion as ancient. However, the source of the selective pressure for the high rate of CCR5 deletion in RCMs remains to be determined. The high allelic frequency of the Delta24 CCR5 in RCMs, in comparison to that of SMs, suggests that R2b-tropism may have been acquired by SIVrcm, as an adaptation to CCR5 genetic defects appeared in its host.
在非洲和美国一家动物园的15只红顶白眉猴（Cercocebus torquatus torquatus）中，有11只的CC趋化因子受体5（CCR5）存在纯合的24个碱基对缺失（Delta24）。CCR5 Delta24缺陷涵盖了第四跨膜区域的八个框内氨基酸。出乎意料的是，11只纯合子之一（Delta24CCR5/Delta24CCR5）的RCM-009被发现自然感染了一种变异的猿猴免疫缺陷病毒（SIV）毒株，该毒株不是R5嗜性的，而是以CCR2b（R2b）作为其主要共受体。SIVrcmGab1是所测试的其他变异SIV中唯一的R2b嗜性SIV。用Delta24 CCR5转染的细胞不支持R5嗜性的SIVmac、SIVcpz、SIVmne、HIV-2或HIV-1进入，并且在β趋化因子介导的信号转导中也无活性。Delta24等位基因频率为86.6%，显著高于在人类中发现的32个碱基对缺失的频率。在34只乌白眉猴（SMs）中，Delta24频率为4.1%，乌白眉猴是一个地理隔离的亚种，自然感染R5嗜性的SIV。在相隔10000年或更久的两个白眉猴亚种中发现相同的缺失，表明Delta24 CCR5缺失是古老的。然而，红顶白眉猴中CCR5高缺失率的选择压力来源仍有待确定。与乌白眉猴相比，红顶白眉猴中Delta24 CCR5的高等位基因频率表明，SIVrcm可能获得了R2b嗜性，作为对其宿主中出现的CCR5基因缺陷的一种适应。
