SUMMARY
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 inflammation. Here, we present an induced pluripotent
stem cell (iPSC)-derived hepatocyte-like cell (HLC) platform to define the hepato-intrinsic response to EBOV infection.We used this platform
to show robust EBOV infection, with characteristic ultrastructural changes and evidence for viral replication. Transcriptomics analysis
revealed a delayed response with minimal early transcriptomic changes, followed by a general downregulation of hepatic function
and upregulation of interferon signaling, providing a potential mechanism by which hepatocytes participate in disease severity and liver
damage. Using RNA-fluorescence in situ hybridization (FISH), we showed that IFNB1 and CXCL10 were mainly expressed in non-infected
bystander cells. We did not observe an inflammatory signature during infection. In conclusion, iPSC-HLCs are an immune competent
platform to study responses to EBOV infection.
Work from the Murphy Lab’s Aging Team featured in Nature!
What’s the secret to living to 100? Centenarian stem cells could offer clues A bank
