Pasi K J, Sabin C A, Jenkins P V, Devereux H L, Ononye C, Lee C A
Department of Haematology, Katharine Dormandy Haemophilia Centre, Royal Free and University College Medical School, London, UK.
Br J Haematol. 2000 Oct;111(1):136-42. doi: 10.1046/j.1365-2141.2000.02325.x.
The chemokine receptor CCR5 is an important co-receptor for cell fusion. A 32-bp deletion of the CCR5 gene, leading to complete absence of functional CCR5 expression, has been associated with resistance to human immunodeficiency virus (HIV) infection in homozygotes and slower HIV disease progression in heterozygotes. The objectives of this study were to assess the effects of this 32-bp deletion on transmission of HIV infection and on HIV disease progression in haemophilic individuals. Six HIV-negative patients from our centre, known to have been exposed to infectious factor VIII concentrates, have been analysed. Three of these patients possess the CCR5 32-bp deletion, two patients being homozygous. The presence of the CCR5 32-bp gene deletion has also been analysed in 71 HIV-positive patients. In this group of patients, there was a lower than expected incidence of the 32-bp deletion. Those who possess the 32-bp deletion progress to AIDS more slowly than those who do not (P = 0.05, log-rank test). Rates of CD4 loss were slower in those heterozygous for the gene deletion. We confirm that heterozygosity for the 32-bp gene deletion in CCR5 is partially protective against initial infection with HIV. In those heterozygous patients who became infected with HIV, disease progression was slower.
趋化因子受体CCR5是细胞融合的重要共受体。CCR5基因32碱基对缺失导致功能性CCR5表达完全缺失，这与纯合子对人类免疫缺陷病毒（HIV）感染的抗性以及杂合子中HIV疾病进展较慢有关。本研究的目的是评估这种32碱基对缺失对血友病个体中HIV感染传播及HIV疾病进展的影响。我们对来自本中心的6名已知接触过感染性凝血因子VIII浓缩物的HIV阴性患者进行了分析。其中3名患者存在CCR5 32碱基对缺失，2名患者为纯合子。我们还对71名HIV阳性患者进行了CCR5 32碱基对基因缺失分析。在这组患者中，32碱基对缺失的发生率低于预期。携带32碱基对缺失的患者比未携带的患者进展为艾滋病的速度更慢（P = 0.05，对数秩检验）。基因缺失杂合子患者的CD4细胞丢失率较慢。我们证实，CCR5基因32碱基对缺失杂合性对HIV初始感染具有部分保护作用。在那些感染HIV的杂合子患者中，疾病进展较慢。
