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人免疫缺陷病毒的受体与辅助受体

时间:2006-11-28栏目:中医学论文

,它们也是趋化因子的受体。趋化因子及其受体在体内的作用是指导特定的白细胞(Leukocyte)向炎症部位转移。所有T细胞趋化剂(chemoattractant)都选择地吸附记忆/被活化的T细胞。CCR5是β-趋化素Rantes、MIPα和MIPβ的受体,其中MIP-1β使用CCR5作为主要受体,而其它趋化素除识别CCR5之外还识别另外一些受体。竞争实验表明MIP-1β可与HIV竞争CCR5受体,阻止病毒与细胞融合[15]。动物实验显示Rantes可以增加巨噬细胞对病毒的抗性。CXCR4是SDF-1的受体,SDF-1可抑制T-trop的HIV;识别CXCR4的单克隆抗体可以抑制由SDF-1诱导产生细胞趋化性和细胞内钙的改变[17]。
因此,在进行治疗时运用多肽或其配体来封闭CCR5,或者通过基因治疗来干扰CCR5基因的表达,用识别辅助受体表位的疫苗来预防HIV的感染,需要建立动物模型来试验针对辅助受体的治疗,因为HIV在非人源细胞中复制较差,并且还需要克服HIV进入动物细胞的障碍。CCR5也是猿猴免疫缺陷病毒(SIV)的辅助受体,但SIV株系的特性与T-trop相似,而与M-trop相异[18],因而利用猿猴进行试验不能完全反映HIV-1在体内的情况,所以有人提出利用产生人CD+4 CCR5的转基因小鼠来进行疫苗试验[18]。
HIV gp120与CCR5的相互作用对中和抗体较为敏感,大部分抗体不能阻止gp120与CD4分子的结合,而能阻止与CCR5的结合。因为CCR5是人体中的正常成分,其免疫原性较差,所以也就不能直接用它作为疫苗,但可以用CCR5蛋白来筛选人源抗体库,抗体库具有广泛的多样性,理论上任何抗原都能筛选到相应的抗体。利用β-趋化素在体外可以阻止HIV-1感染,据说在体内用β-趋化素进行治疗时,需将β-趋化素进行修饰,否则会使人体引起炎症反应[19]。

作者单位:中国科学院微生物研究所分子病毒室,北京 100080

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