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. 2017 Aug 15;7:8267. doi: 10.1038/s41598-017-07434-y

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Minimal intrahepatic interferon-stimulated gene induction in HEV infected human-liver chimeric mice, between weeks 2 to 14 post infection. Whole chimeric-liver RNA was isolated from HEV gt3 and gt1 infected mice and analyzed for the human specific gene expression of sensing molecules TLR3 and DDX58 (a), transcription factor STAT1 (b), and interferon stimulated genes CXCL9, CXCL10, ISG15, RSAD2, OAS1, MX1 and IFIT1 (c) using qRT-PCR. Groups consist of n = 4, 6, 4, 3, 6 and 4 mice from left to right (a–c). Given values on y-axes are fold changes over HEV RNA negative chimeric-livers transplanted with the same hepatocyte donor. X-axes shows weeks post infection, HEV genotype, and hepatocyte donor. Significance was assessed within groups of the same hepatocyte donor using Krukskal-Wallis one-way Anova with Dunnett’s Multiple comparison test. *P < 0.05, Gray bars indicate HEV gt1, black bars HEV gt3 (a–c). In-depth human gene expression analysis was performed on RNA from chimeric mouse livers before infection, and after 2, 6 and 14 weeks of HEV gt3 infection using nCounter® Human Immunology V2 panel. Principal component 1 (x-axis) and 2 (y-axis) comprise 49% of the variance between samples using all non-cross reactive genes (d). Uninfected samples are indicated in green, infected samples are indicated in blue, red (HEV0069), purple (HEV0122) and yellow and by the number of weeks infected HEV2, HEV6, HEV6, HEV14, respectively (d). Heatmap shows fold change over average of 4 uninfected mice for interferon signaling and response genes (e). Gene legend is indicated on the right side and sample legend below the heatmap (e). Dark red indicates ≥ 5 fold change, and dark blue ≤ 5 fold change (e).