Peptidic HIV-1 fusion inhibitor VIR576 as a potential dual-functional microbicide inhibits antigen-specific CD4 + T-cell activation
10.3969/j.issn.1673-4254.2014.05.01
- VernacularTitle: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
- Author:
Minmin LI
1
;
Ruitao ZHANG
;
Yiping HU
;
Jianjun LI
;
Shibo JIANG
;
Xiaojuan LI
;
Shuwen LIU
Author Information
1. 暨南大学附属第一医院
- Keywords:
HIV-1 fusion inhibitor;
gp41;
fusion peptide;
VIR576;
CD4+T cell activation
- From:
Journal of Southern Medical University
2014;(5):597-602
- CountryChina
- Language:Chinese
-
Abstract:
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.
