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...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.展开更多
基金Supported by National Natural Science Foundation of China(30672496 and 30801413)Guangdong Medical Research Grant(A201032)Guangdong International Cooperation Grant(2011B050200006)
文摘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.
