Homo sapiens isolate:H9 HESCs (WA09) Transcriptome or Gene expression

Dengue virus (DENV) infection causes profound changes in the host cells and these changes underlie the immune response-based viral clearance and pathogenesis. There are several major cell/tissue types relevant for DENV pathogenesis in vivo, including immune cells, liver, and vascular endothelial cells. We applied a directed differentiation system that produces hepatocyte-like cells (HLCs) from pluripotent stem cells to investigate various aspects of DENV- hepatic cells interaction. Human embryonic stem cells were resistant to DENV infection while progeny hepatic cells were permissive. The transition to DENV permissiveness coincided with the upregulation of entry factors for the virus. Infection of HLCs by DENV was self-limiting due to the activation of the interferon (IFN) pathways, which protected by-stander cells from infection but failed to induce the same level of interferon-induced genes (ISGs) expression in the infected cells due to the subversion of IFN signaling by DENV. Innate immunity also protected the infected cells from virus-induced apoptosis. Furthermore, DENV infection activated the NF-?B pathway, increased production of reactive oxidative species (ROS), and led to production of inflammatory cytokines which may contribute to the cytokine storm implicated in dengue hemorrhagic fever (DHF). Finally, DENV infection of HLCs resulted several in vitro phenotypes that may have relevance for acute liver failure and vascular permeability during DHF. These include the disruption of adherens junctions and the downregulation of many liver specific genes such as albumin (ALB) and coagulation factor V (F5).

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