Abstract
Viral hepatitis, the leading cause of liver diseases worldwide, is induced upon infection with hepatotropic viruses, including hepatitis A, B, C, D, and E virus. Due to their obligate intracellular lifestyles, culture systems for efficient viral replication are vital. Although basic and translational research on viral hepatitis has been performed for many years, conventional hepatocellular culture systems are not optimal. These studies have greatly benefited from recent efforts on improving cell culture models for virus replication and infection studies. Here we summarize the use of human stem cell-derived hepatocyte-like cells for hepatotropic virus infection studies, including the dissection of virus-host interactions and virus-induced pathogenesis as well as the identification and validation of novel antiviral agents.
Highlights
Viral hepatitis manifests itself as continuous liver inflammation and eventually liver injury and hepatic failure
An alternative treatment approach that we are currently exploring is based on the use of nonpathogenic adeno-associated viruses (AAV) combined with CRISPR-Cas9 to deliver short hairpin RNA to downregulate hepatitis E virus (HEV) replication
hepatocyte-like cells (HLCs) derived from hiPSC or human embryonic stem cells (hESCs) provide a promising tool to study the biology of hepatotropic viruses and to screen novel antiviral treatments in the future
Summary
Viral hepatitis manifests itself as continuous liver inflammation and eventually liver injury and hepatic failure. Most hepatoma cell lines lack various functional enzymes, such as CYP450 and other phase I, II, and III drug-metabolizing enzymes, which make them unsuited for the assessment of antiviral drug interactions and metabolism [9, 10] Studies using these models are limited in their ability to mimic natural virusinduced pathologies in the liver. Given the limitations and challenges of using hepatoma cells and PHHs, hepatocyte-like cells (HLCs) derived from human embryonic stem cells (hESCs) or induced pluripotent stem cell (iPSC) have emerged as a promising cell culture model to study basic and translational liver diseases as well as hepatitis virus infection [12,13,14]. We summarize the current knowledge on cell culturebased models available for these viruses and highlight the advantages of HLCs derived from stem cell as an improved system for basic and translational viral hepatitis research
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