Peptidic HIV-1 fusion inhibitor VIR576 as a potential dual-functional microbicide inhibits antigen-specific CD4 + T-cell activation
LI Minmin
ZHANG Ruitao
HU Yiping
LI Jianjun
JIANG Shibo
LI Xiaojuan
LIU Shuwen
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.
Keywords：HIV-1 fusion inhibitorgp41fusion peptideVIR576CD4+T cell activation
Publication Date：2014-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 597-602 )