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.