Peptidic HIV-1 fusion inhibitor VIR576 as a potential dual- functional microbicide inhibits antigen-specific CD4(+) T-cell activation / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>