Ebola virus infection induces a type I interferon response and the shutdown of key liver functions in human iPSC-derived hepatocytes

Abstract

Liver damage and an exacerbated inflammatory response are hallmarks of Ebola virus (EBOV) infection. Little is known about the intrinsic response to infection in human hepatocytes and their contribution to the observed inflammatory response. Here, we present an iPSC-derived hepatocyte platform to define the hepato-intrinsic response to EBOV infection. Transcriptomics analysis revealed a delayed host response with minimal transcriptomic changes at one day post infection (dpi) followed by a general downregulation of genes associated with hepatic functions and upregulation of interferon signaling at two and three dpi. Using RNA-FISH, we showed at single cell resolution that IFNβ and CXCL10 were mainly expressed in bystander cells or cells with weak EBOV mRNA signal intensity. We did not observe an inflammatory signature at any timepoint. In conclusion, iPSC-derived hepatocytes are an immune competent platform to study intrinsic responses to EBOV infection that have not been observed in EBOV-infected hepatocarcinoma cell lines.