Ebola is a deadly virus that causes fever, body aches, diarrhea, and sometimes bleeding inside and outside the body. It triggers a system-wide inflammation and fever and can also damage many types of tissues in the body, either by prompting immune cells such as macrophages to release inflammatory molecules or by direct damage: invading the cells and consuming them from within. However, the consequences are especially profound in the liver and it is not fully understood how liver cells respond to Ebola virus infection. Now, researchers from Boston University School of Medicine used stem cell biology to provide insights into Ebola virus infection.
The findings are published in the journal Stem Cell Reports in an article titled, “Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes.”
“Liver damage and an exacerbated inflammatory response are hallmarks of Ebola virus (EBOV) infection,” wrote the researchers. “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.”
The research led by Gustavo Mostoslavsky, MD, PhD, associate professor of medicine and microbiology; Elke Mühlberger, PhD, professor of microbiology; and colleagues from Boston University School of Medicine harnessed stem cell biology to obtain an inexhaustible source of human liver cells, so-called hepatocyte-like cells (HLCs), derived from induced pluripotent stem cells.
The stem cell-derived HLCs closely resembled primary liver cells and could be readily infected by Ebola virus in the lab.
Infected cells did not die, but they did shut down genes required for proper HLC function.
Further, Ebola virus-infected immune cells could transfer the virus to HLCs in co-cultures, suggesting that infected immune cells may act as virus shuttles in patients. This stem cell-derived liver cell model will be a valuable tool for future studies on Ebola virus liver pathology and potential therapeutic interventions.
“The data presented here corroborate that genes associated with liver function are perturbed in EBOV-infected hepatocytes. Future studies using this platform can help identify how EBOV impairs liver function during disease progression and inform the development of therapeutic interventions that may universally prevent EBOV fatality,” concluded the researchers.