At the level of entry, four cellular entry factors are required for HCV uptake—cluster of differentiation (CD)81, scavenger type B class I (SCARB1), claudin 1 (CLDN1), and occludin (OCLN)—but only CD81 and OCLN have to be of human origin for entry into murine cell lines.11 This discovery was recently translated into the first inbred mouse model for the early stages of HCV infection.12 RNA replication in mouse hepatoma cells does not seem to be restricted by dominant negative factors.13 In fact, stable, albeit low-level, HCV RNA replication

can be established in hepatic and nonhepatic murine cell lines harboring subgenomic or full-length drug-selectable replicons.14, 15 These data suggest that all essential cellular factors required for HCV replication are present in mouse Proteases inhibitor cells, but that the viral proteins may not optimally interact with the murine orthologs. An additional limitation to HCV replication in murine cells may relate to antiviral defense mechanisms. For example, the viral protease cleaves critical immune-signaling intermediates TRIF and MAVS in humans, but it is not known whether this evasion mechanism occurs in mouse cells. Indeed, HCV RNA replication is more efficient in mouse cells lacking Selleck PKC412 immune sensors, such as PKR,16 or transcription factors, such as IRF3.17 Long et al. provide the first evidence that mouse cells can support the late

stages for the HCV life cycle, if critical components of the VLDL pathway are present. Expression of either human or mouse apoE dramatically increases packaging efficiency, indicating that apoE is not a species-specific restriction factor.

Furthermore, although the murine hepatic cell line reported here was deficient in apoE, primary murine hepatocytes assayed in parallel boasted high expression, suggesting that this host factor would not be limiting in mouse models in vivo. Still, the investigators note that additional host factors may be lacking, inhibitory, or incompatible with HCV assembly in primary murine hepatocytes not evident in murine hepatic cell lines. This highlights the effect of the cell-culture system chosen for analysis, and emphasizes that cell lines or in vitro models often do not recapitulate primary cell or in vivo phenotypes. Nonetheless, Edoxaban these important findings by Long et al. shed light on HCV assembly and further raise the hope that an inbred mouse model for HCV infection can be achieved. 1 “
“This chapter discusses the background, prevention, diagnosis, treatment and prognosis of pregnancy-related liver disease. Pregnancy-related liver diseases can be classified as hyperemesis gravidarum (HG), intrahepatic cholestasis of pregnancy (ICP), pre-eclampsia and eclampsia, HELLP syndrome and acute fatty liver of pregnancy (AFLP). Regular pre-natal visits and screening for pre-eclampsia/ICH lead to early diagnosis and treatment especially in high risk patients and those with a family history.