Fig. 1: Design and characterization of an autonomous, intelligent, virus-inducible immune-like sensor (ALICEsen).
From: Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice
a Schematic illustration of the design principle for a virus sensor (ALICEsen). Virus infects mammalian cells and releases its nucleic acid into the cytoplasm, which activates the destabilized STING (pYW274). Activated STING triggers a synthetic immune signaling pathway mediated by endogenous tank-binding kinase 1 (TBK1), resulting in activating phosphorylation and dimerization of endogenous interferon regulatory factor 3 (IRF3), which translocates into the nucleus as a dimer and initiates the expression of a given gene of interest (GOI) under the control of a “virus-inducible promotor (PALICE×)” sequence. b Fold change of SEAP in ALICEsen induced by different STING-suppression/activation viruses. pYW274/pWS67-transgenic cells were incubated with different viruses as indicated, and SEAP in supernatant was quantified at 2 and 4 dpi (day post-infection). c HSV-1-dependent EGFP expression in ALICEsen. pYW274/pYW379-transgenic HEK-293T cells were incubated with different titers of HSV-1 (MOI = 0–10) and quantified at 2 dpi. d Time-dependent SEAP production kinetics of ALICEsen. HEKALICE-SEAP stable cell lines were incubated with HSV-1 (MOI = 0.5) for different incubation times. SEAP levels in culture supernatants were quantified at the indicated time points. e HSV-1-dependent SEAP production kinetics of ALICEsen. pYW274/pWS67-transgenic HEK-293T cells were incubated with different titers of HSV-1. White bars (1 day), blue bars (2 day), red bar (3 day). P values for all other groups versus HSV-1 (MOI = 0) group on the same day. f HSV-1-inducible SEAP production in various mammalian cell lines. g–n Virus-inducible IFN-α/IFN-β production in ALICEim. P values for virus group versus Vehicle group. o qPCR analysis of viral genes in ALICEim. White circles (ALICEsen-SEAP), blue circles (ALICEim-IFNα), red circles (ALICEim-IFNβ). P values for all other groups versus ALICEsen-SEAP group in the same virus. Data in b-o are expressed as means ± SD; n = 3 independent experiments in b, d–o; n = 3 or 4 independent experiments in (c); P values in e, o were calculated by two-way ANOVA with Bonferroni’s post hoc test; P values in g–n were calculated by two-tailed unpaired t-test; n.s. not significant. Source data are provided as a Source Data file.
