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. 2017 Jun 19;7:3821. doi: 10.1038/s41598-017-04186-7

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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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HCV infection results in IFN-λ4 expression and IFN-α unresponsiveness that is restored by DAA treatment. (A) PHHs were infected with JFH1 HCVcc at 2 MOI. Shortly after HCV infection, telaprevir (5 μM) plus sofosbuvir (5 μM) were added to HCV-infected cells. After 24 or 48 hours, the cells were harvested, and gene expression was analysed by real-time qPCR. (B) PHHs with the IFNL4 ΔG/ΔG genotype were infected with JFH1 HCVcc at 2 MOI. Six hours after HCV infection, the culture medium was changed to the medium containing telaprevir (5 μM) and sofosbuvir (5 μM). After 120 hours, the cells were treated with 100 IU/ml of IFN-α for 30 minutes (B) or 6 hours (C). The cells were harvested, and gene and protein expression were analysed by immunoblotting (B) or real-time qPCR (C). Data are presented as means ± S.E.M. ***P ≤ 0.001 (Student’s t-test). DAA: direct-acting antivirals. All the data are representative of two independent experiments. Full-length blots of PY-STAT1 (B) with multiple exposure times are included in the Supplementary Fig. 9B. The data are representative of three independent experiments.