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  • Although our model supported viral

    2018-11-08

    Although our model supported viral life cycle, there were key elements of the system that required more detailed attention. Despite robust infection, hESC-Heps and primary hepatocytes produce less infectious virions than Huh7 line (Liang et al., 2009; Ploss et al., 2010; Podevin et al., 2010; Roelandt et al., 2012; Wu et al., 2012). We hypothesized the lesser infection of hESC-Heps may be due to a robust induction of cellular immunity. Indeed, after HCV infection, hESC-Heps demonstrated strong induction of IL-29, followed by IFN-stimulated gene (ISG) expression. This was lesser in Huh7 ANA 12 and is likely attributable to defects in retinoic acid-inducible gene 1 (RIG-1) pathway (Sumpter et al., 2005). These observations were tested extensively in vitro, and further supported by studies in which extraneous RNA was introduced to the cells to stimulate the IFN response (Park et al., 2012). In conclusion, although infection in hESC-Heps has been established, it is relatively low (Roelandt et al., 2012; Wu et al., 2012). Prior to these studies, the reason for this had proved elusive. We provide evidence that by modulating the JAK/STAT pathway and the downstream IFN response, hESC-Hep infection and subsequent replication is “tunable.” This, in combination with the scalable nature of our system and the defined genetics, provides the field with an important model and platform technology.
    Experimental Procedures
    Author Contributions
    Acknowledgments
    Main Text (Stem Cell Reports 2, 838–852, June 3, 2014) An inadvertent production error occurred after the proof stage while setting Table 1 for print. As a result, the labels “GFP Negative,” “GFP Positive,” and “Total” were positioned incorrectly. We apologize for this mistake and provide a corrected version of Table 1 below. The online version has also been corrected.
    Main Text (Stem Cell Reports 2, 910–924, June 3, 2014) In Figure 3D of this article as originally published, a fluorescent image of the spleen panel was missing. The corrected Figure 3 is shown here and has been replaced online.