title: Modeling Dengue Virus-Hepatic Cell Interactions Using Human Pluripotent Stem Cell-Derived Hepatocyte-like Cells.
abstract: The development of dengue antivirals and vaccine has been hampered by the incomplete understanding of molecular mechanisms of dengue virus (DENV) infection and pathology, partly due to the limited suitable cell culture or animal models that can capture the comprehensive cellular changes induced by DENV. In this study, we differentiated human pluripotent stem cells (hPSCs) into hepatocytes, one of the target cells of DENV, to investigate various aspects of DENV-hepatocyte interaction. hPSC-derived hepatocyte-like cells (HLCs) supported persistent and productive DENV infection. The activation of interferon pathways by DENV protected bystander cells from infection and protected the infected cells from massive apoptosis. Furthermore, DENV infection activated the NF-κB pathway, which led to production of proinflammatory cytokines and downregulated many liver-specific genes such as albumin and coagulation factor V. Our study demonstrates the utility of hPSC-derived hepatocytes as an in vitro model for DENV infection and reveals important aspects of DENV-host interactions.
authors.affiliation: Department of Biological Science, Florida State University, 319 Stadium Drive, Tallahassee, FL 32306-4295, USA.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Lang
authors.affiliation: Center for Genomics and Personalized Medicine, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vera
authors.affiliation: Department of Biological Science, Florida State University, 319 Stadium Drive, Tallahassee, FL 32306-4295, USA.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Biological Science, Florida State University, 319 Stadium Drive, Tallahassee, FL 32306-4295, USA. Electronic address: tang@bio.fsu.edu.
authors.forename: Hengli
authors.initials: H
authors.lastname: Tang
mesh_terms: D017209:Apoptosis; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003715:Dengue / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003716:Dengue Virus / Q000502:physiology*; D005165:Factor V / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D000075462:Serum Albumin, Human / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D005165:Factor V; D007372:Interferons; D020794:Receptor Protein-Tyrosine Kinases; D000075462:Serum Albumin, Human; D000094963:Axl Receptor Tyrosine Kinase