Author: Ishibashi, Daisuke; Homma, Takujiro; Nakagaki, Takehiro; Fuse, Takayuki; Sano, Kazunori; Satoh, Katsuya; Mori, Tsuyoshi; Atarashi, Ryuichiro; Nishida, Noriyuki
Title: Type I interferon protects neurons from prions in in vivo models Document date: 2019_2_7
ID: zopwlaq4_39
Snippet: I-IFN, which defends the host against infectious agents, is produced not only by immune cells but also by other cell types including fibroblasts and neurons (Delhaye et al., 2006) . Hence, we investigated the potential anti-prion effect of recombinant I-IFNs (IFN-and -b) in cell culture models. In the primary prion-challenge test IFN-b treatment significantly suppressed PrP Sc levels in persistently 22 L-prion-infected cells, and pretreated cells.....
Document: I-IFN, which defends the host against infectious agents, is produced not only by immune cells but also by other cell types including fibroblasts and neurons (Delhaye et al., 2006) . Hence, we investigated the potential anti-prion effect of recombinant I-IFNs (IFN-and -b) in cell culture models. In the primary prion-challenge test IFN-b treatment significantly suppressed PrP Sc levels in persistently 22 L-prion-infected cells, and pretreated cells became resistant to 22 L-prion primary infection in a dose-dependent manner; the effect of IFN-at similar doses was weaker ( Fig. 2A and B ). Similar resistance to prion was also observed in IFN-b-overexpressing stable cell lines (58-IFN-b) ( Fig. 2C and Supplementary Fig. 2A) . Transient IFN-b expression did not reduce endogenous PrP Sc levels in persistently 22 L prion-infected cells (Supplementary Fig. 2C ). Pre-transfection of cells with Poly I:C, which activates the innate immune system via I-IFN induction, prevented the establishment of prion infection in a dose-dependent manner (Fig. 2D) . To evaluate efficacy of IFN-b against prion propagation in prion infectious animal model, we performed bioassay using 22 L-prion-infected Tga20 mice with lentivirus coding Ifnb gene (LV-IFN). Lentiviral vectors were administered at 3 weeks after prion infection. LV-IFN localized in thalamus at 20 days after stereotaxic injection into Tga20 mice brain (Fig. 2E ). When lentivirus carrying the mouse Ifnb gene (LV-IFN) was injected intracerebrally, PrP Sc levels were significantly reduced at the terminal stage in the brain of Tga20 mice after prion inoculation (Fig. 2F) . In pathological analysis, vacuolation and PrP Sc deposits decreased significantly in the brains of LV-IFN-treated mice ( Supplementary Fig. 2B ). The endogenous PrP C level did not change in response to IFN-b overexpression in N2a-58 cells ( Supplementary Fig. 2D ), indicating that IFNb might prevent new PrP Sc production at the early phase of primary prion infection without affecting PrP C expression.
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