Tiensiwakul Pornthep
Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Intervirology. 2004;47(2):87-92. doi: 10.1159/000077831.
It is known that a 32-bp-deleted CCR5 mutant (CCR5-Delta32) plays a critical role in resistance to human immunodeficiency virus type 1 (HIV-1) infection. We became aware of a number of seronegative patients at high risk of HIV-1 infections. Since CCR-Delta32 is not found in Thais, we examined the role of stromal cell-derived factor (SDF) 1-3'A polymorphism in resistance to HIV-1 in seronegative Thai prostitutes at high risk.
We determined CCR5-Delta32 by PCR, SDF1-3'A by RFLP, and plasma SDF-1 level by sandwich ELISA.
We did not find any CCR-Delta32 mutant in 432 subjects. In our SDF1-3'A genotyping, we found allelic frequencies of 0.406, 0.199, and 0.289 in HIV-1-seronegative prostitutes at high risk, HIV-1-seropositive patients, and normal blood donors, respectively. There was a significant difference in the allelic frequencies of SDF1-3'A between HIV-1-seronegative prostitutes at high risk and HIV-1-seropositive patients (p < 0.005). Striking differences were seen in homozygotes (SDF1-3A/3A); 20.3% in HIV-1-seronegative patients at high risk compared with 2.5% in HIV-1-seropositive patients. In addition, we showed that the plasma SDF1 level in the HIV-1-seronegative prostitutes at high risk was twice that found in normal blood donors (p = 0.005), and even higher than that of HIV-1-seropositive patients (p = 0.002).
The finding is relevant as regards the fact that SDF1-3'A polymorphism induces an increase of SDF1 chemokine production, in which it competes with HIV-1 in binding to CXCR4 receptor, and in turn inhibits HIV-1 infection. The SDF1-3'A-mediated resistant mechanism in Thais differs from that of CCR5-Delta32-mediated resistance in Caucasians. This study provides the first evidence for SDF-3'A polymorphism in resistance to HIV-1 infection in Thais, and may represent the resistant mechanism in the extremely rare CCR5-Delta32 mutant of other ethnic groups such as Africans and Japanese.
已知一种缺失32个碱基对的CCR5突变体（CCR5 - Delta32）在抵抗1型人类免疫缺陷病毒（HIV - 1）感染中起关键作用。我们注意到一些有HIV - 1感染高风险的血清学阴性患者。由于泰国人未发现CCR - Delta32，我们研究了基质细胞衍生因子（SDF）1 - 3'A多态性在有高风险的血清学阴性泰国妓女抵抗HIV - 1中的作用。
我们通过聚合酶链反应（PCR）测定CCR5 - Delta32，通过限制性片段长度多态性（RFLP）测定SDF1 - 3'A，通过夹心酶联免疫吸附测定（ELISA）测定血浆SDF - 1水平。
在432名受试者中未发现任何CCR - Delta32突变体。在我们的SDF1 - 3'A基因分型中，在有高风险的HIV - 1血清学阴性妓女、HIV - 1血清学阳性患者和正常献血者中，等位基因频率分别为0.406、0.199和0.289。有高风险的HIV - 1血清学阴性妓女与HIV - 1血清学阳性患者之间SDF1 - 3'A的等位基因频率存在显著差异（p < 0.005）。纯合子（SDF1 - 3A/3A）中存在显著差异；有高风险的HIV - 1血清学阴性患者中为20.3%，而HIV - 1血清学阳性患者中为2.5%。此外，我们发现有高风险的HIV - 1血清学阴性妓女的血浆SDF1水平是正常献血者的两倍（p = 0.005），甚至高于HIV - 1血清学阳性患者（p = 0.002）。
这一发现具有重要意义，因为SDF1 - 3'A多态性可诱导SDF1趋化因子产生增加，在与HIV - 1竞争结合CXCR4受体中发挥作用，进而抑制HIV - 1感染。泰国人中SDF1 - 3'A介导的抗性机制与白种人中CCR5 - Delta32介导的抗性机制不同。本研究首次提供了泰国人SDF - 3'A多态性在抵抗HIV - 1感染中的证据，并且可能代表了非洲人和日本人等其他种族极罕见的CCR5 - Delta32突变体中的抗性机制。
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