Functional innate immunity restricts Hepatitis C Virus infection in induced pluripotent stem cell-derived hepatocytes

Scientific Reports
Anja SchöbelEva Herker

Abstract

Knowledge of activation and interplay between the hepatitis C virus (HCV) and the hosts' innate immunity is essential to understanding the establishment of chronic HCV infection. Human hepatoma cell lines, widely used as HCV cell culture system, display numerous metabolic alterations and a defective innate immunity, hindering the detailed study of virus-host interactions. Here, we analysed the suitability of induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (iHLCs) as a physiologically relevant model to study HCV replication in vitro. Density gradients and triglyceride analysis revealed that iHLCs secreted very-low density lipoprotein (VLDL)-like lipoproteins, providing a putative platform for bona fide lipoviroparticles. iHLCs supported the full HCV life cycle, but in contrast to Huh7 and Huh7.5 cells, replication and viral RNA levels decreased continuously. Following HCV infection, interferon-stimulated gene (ISG)-expression significantly increased in iHLCs, whereas induction was almost absent in Huh7/7.5 cells. However, IFNα-stimulation equally induced ISGs in iHLCs and hepatoma cells. JAK-STAT pathway inhibition increased HCV replication in mature iHLCs, but not in Huh7 cells. Additionally, HCV replication ...Continue Reading

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Citations

Jul 10, 2019·Stem Cells International·Jingjing WangYuchen Xia
Apr 5, 2020·Nature Communications·Viet Loan Dao ThiCharles M Rice
Dec 24, 2018·Trends in Microbiology·Usama AshrafNadia Naffakh
Jul 3, 2020·Cells, Tissues, Organs·Jia YaoScott L Nyberg

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Methods Mentioned

BETA
density gradient centrifugation
density gradient centrifugations
dissect
FCS
PCR
confocal microscopy
in vitro transcription
Assay

Software Mentioned

R
Fiji
GraphPadPrism
RStudio

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