A study uncovers how Ebola and Marburg viruses damage the human gut
Ebola virus (EBOV) and Marburg virus (MARV) are extremely deadly pathogens that cause widespread illness, including significant harm to the gastrointestinal tract. Severe diarrhea and the resulting dehydration are major contributors to death in EBOV and MARV infections, yet the specific role of the intestinal lining in these outcomes has not been fully understood.
Led by Elizabeth Yvonne Flores, PhD, a recent BU Chobanian & Avedisian School of Medicine graduate, and conducted at BU’s National Emerging Infectious Diseases Laboratories (NEIDL) and the Center for Regenerative Medicine (CReM) at BU and Boston Medical Center, a new study sheds light on the mechanisms behind this damage. The research shows that both EBOV and MARV can infect and replicate inside human gut epithelial cells and disrupt the cells’ ability to regulate fluid secretion, mirroring the severe symptoms seen in patients.
“This work deepens our understanding of how filovirus infections harm the gut and points to potential cellular pathways that could be targeted for treatment,” says Elke Mühlberger, PhD, co-corresponding author and professor of virology, immunology & microbiology, as well as an investigator at BU’s NEIDL. “It also underscores how valuable iPSC-derived organoids are for studying viral diseases.”
To study human gut tissue in a controlled setting, the researchers created organoids—small, three-dimensional structures that replicate human intestinal and colonic tissue—from induced pluripotent stem cells (iPSCs). iPSCs are adult cells reprogrammed in the lab to behave like stem cells. The researchers then infected these “mini-guts” with EBOV and MARV and observed that the viruses could multiply within the tissue.
By examining gene activity in the infected organoids, the team found that organoids modeling the small intestine and those modeling the colon responded differently to infection, with the colon-like organoids showing more pronounced dysfunction. The infections disrupted key signaling pathways that govern ion and fluid transport in the gut and damaged the intestinal lining’s architecture, including the apical surface (the cell’s outermost layer) and junctional components that control what passes through the intestinal wall. These changes help explain how the viruses cause substantial fluid loss and life-threatening diarrhea. The infected mini-guts also exhibited a delayed innate immune response, particularly in the production of interferon-stimulated genes that normally help combat viral infections.
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“The organoid platform successfully captures key features of human GI pathology, making it a powerful tool for future research into host-pathogen interactions and for identifying potential therapeutic targets to treat these deadly diseases,” notes Gustavo Mostoslavsky, MD, PhD, co-author of the study and a professor of medicine and virology, immunology & microbiology, as well as co-director of CReM at BU.
The study is published online in PLOS Pathogens.
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