尿激酶体外抑制人体免疫缺损病毒的侵染能力(英文)  

Urokinase Inhibits Infectivity by HIV-1 in vitro

作　　者：刘建宁[1,2] 张德正[1,2] Carole LeContel 陈平[1] Victor Gurewich 张菁[1] 陈新园[1] 

机构地区：[1]南京大学分子医学研究所,南京210093 [2]哈佛大学哈佛医学院 [3]INSERM,法国马赛13000

出　　处：《南京大学学报（自然科学版）》2005年第5期451-461,共11页Journal of Nanjing University（Natural Science）

摘　　要：人体免疫缺损病毒的包膜蛋白gp120的V3环区包含一段在人类蛋白质中很少出现的高度保守序列,但这段序列与纤溶酶原被纤溶酶原激活剂酶切位点附近序列有同源性.由于V3环区在人体免疫缺损病毒侵染细胞过程中的重要性,评估了尿激酶对人体免疫缺损病毒侵染能力的影响.通过检测逆转录酶活力,P24抗原的表达和合胞体形成情况发现尿激酶可以抑制人体免疫缺损病毒对多种淋巴瘤和白血病细胞系,如MT4、CEM、H9和外周血单核细胞的侵染能力,并且这种抑制与尿激酶浓度呈剂量依赖关系.那些能够被尿激酶抑制的人体免疫缺损病毒株其V3环区序列必须与纤溶酶原激活区序列同源,实验室常用病毒株包括BRU和RF以及某些野生病毒株.研究结果显示尿激酶在体外实验中可以抑制人体免疫缺损病毒的侵染能力.The V3 loop of the envelope protein, gp120, of HIV-1 contains a highly conserved motif, which is rare in human proteins, but we noted that it was homologous to the activation site loop of plasminogen that is cleaved by plasminogen activators. Since the V3 loop is important to cell entry of HIV-1, the effect of urokinase on HIV-1 infectivity was evaluated. When HIV 1 in culture medium was exposed to a range of concentrations of urokinase, a dose-dependent inhibition of infectivity was observed in a variety of lymphoma and leukemia call lines including MT4, CEM, H9, and peripheral bloot mononuclear calls using assays for reverse transcriptase, P24 antigen and syncytia formation. The HIV-1 strains inhibited by UK were those whose V3 loops were homologous to plasminogen and included the laboratory strains BRU and RF, as well as certain wild strains. In conclusion, the present study shows that UK inhibits infectivity by HIV-1 in vitro.

关 键 词：尿激酶 HIV-1 GP120 V3环区 纤溶酶原 人体免疫缺损病毒 

分 类 号：Q78[生物学—分子生物学]