HIV进入抑制多肽VIR576可抑制抗原特异性CD4^+T细胞的体外活化:一种潜在的双功能杀微生物剂(英文)  

Peptidic HIV- 1 fusion inhibitor VIR576 as a potential dualfunctional microbicide inhibits antigen- specific CD4^+ T- cell activation

作　　者：李珉珉[1] 张瑞涛[2,3] 胡义平[3] 李建军[3] 姜世勃[4] 李晓娟[3] 刘叔文[3] 

机构地区：[1]暨南大学附属第一医院,广东广州510630 [2]三峡大学医学院药理学部,湖北宜昌443000 [3]南方医科大学药学院,广东广州510515 [4]复旦大学医学院病原微生物研究所教育部医学分子病毒学重点实验室,上海200032

出　　处：《南方医科大学学报》2014年第5期597-602,共6页Journal of Southern Medical University

基　　金：Supported by National Natural Science Foundation of China(30672496 and 30801413);Guangdong Medical Research Grant(A201032);Guangdong International Cooperation Grant(2011B050200006)~~

摘　　要：目的观察VIR576对CD4+T细胞活化的作用。方法分离DO11.10小鼠脾细胞并用OVA或ConA分别刺激,观察VIR576对抗原特异性和非特异性T细胞活化的影响;培养A2b CD4+T细胞株和磁珠分离的DO11.10小鼠脾脏CD4+CD25-效应性T细胞,分别用特异性抗原激活,观察VIR576对抗原特性CD4+T细胞活化的影响。结果 VIR576抑制抗原特异性T细胞的活化,但对非抗原特异性T细胞活化的影响不显著,非特异性T细胞活化不需要TCR和CD3的交联。进一步研究发现,VIR576也可以下调抗原特异性CD4+T细胞的活化。结论粘膜活化的CD4+T细胞对HIV-1高度易感,VIR576不仅具有抑制HIV进入的活性还能够抑制CD4+T细胞活化,提示VIR576是一种有开发潜能的预防HIV性传播的杀微生物剂。Objective To observe if VIR576, an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin （a1-AT） which inhibits human immunodeficiency virus type 1 （HIV-1） entry into the target cells by interacting with fusion peptide （FP）, can also directly inhibit CD4＋T cell activation in vitro. Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation. Both primary CD4＋CD25-T cells from DO11.10 mice and CD4＋T cell line A2b were activated with specific antigens to evaluate the effects of VIR576. Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation, which bypassed the crosstalk between the CD3-signaling complex and TCR. We furthermore observed that VIR576 could also down-regulate antigen-specific CD4＋ T-cell activation. Conclusion Given the high susceptibility of activated CD4＋ T cells in the mucosa to HIV-1 infection, the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4＋T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.

关 键 词：HIV进入抑制多肽 GP41 融合多肽 VIR576 CD4’T细胞活化 

分 类 号：R512.91[医药卫生—内科学]