Peptidic HIV-1 fusion inhibitor VIR576 as a potential dual- functional microbicide inhibits antigen-specific CD4(+) T-cell activation.
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.


CONCLUSIONS
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.
Center for Clinical Laboratory, First Affiliated Hospital of Jinan University, Guangzhou 510630, China. E-mail: limm269@126.com.
Minmin
M
Li
Ruitao
R
Zhang
Yiping
Y
Hu
Jianjun
J
Li
Shibo
S
Jiang
Xiaojuan
X
Li
Shuwen
S
Liu
D000818:Animals; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin; D010446:Peptide Fragments / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D017252:CD3 Complex; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000515:alpha 1-Antitrypsin; D010047:Ovalbumin