Influenza viruses cause seasonal outbreaks—and less frequently, pandemics—in people that put a strain on healthcare systems, and they can also cause outbreaks in animals with significant economic consequences to agriculture. The origin of all influenza viruses is wild aquatic waterfowl (e.g., ducks and geese), where the viruses are found in the gut and shed in the feces. The viruses may then find their way into poultry populations, where infection is either in the gut or the respiratory tract.
People can become infected directly from wild birds or though interactions with poultry, and the disease in people is typically known as “bird flu,” which can be fatal. Moreover, the more people that contract bird flu, the greater the risk that it could start spreading person to person. The intestine of wild aquatic waterfowl, and the intestine and respiratory tract of chickens, are therefore key sites where new influenza virus strains emerge that may be of pandemic potential. However, our understanding of how influenza viruses interact with these organs is limited as live animal studies with poultry and aquatic waterfowl require specialist research facilities.
To address this, a Grand Challenges Grant funded team comprised of Principal Investigator (PI) Assistant Professor of Animal and Avian Sciences Andrew Broadbent (AGNR) and Co-PIs Assistant Professor of Animal and Avian Sciences Younggeon Jin (AGNR) and Associate Professor of Cell Biology and Molecular Genetics Margaret (Meg) Scull (CMNS) set out to develop primary intestinal organoids and respiratory airway cell cultures (essentially mini-guts and mini-tracheas grown in petri-dishes in the lab) from chickens and ducks, and study the interaction of influenza viruses with them, to better understand how new strains emerge.
The team recruited two undergraduate students, a Ph.D. student, and a laboratory technician, and together, the team successfully generated the intestinal organoids from chickens and ducks, and the respiratory airway cultures from chickens. The team then demonstrated that influenza viruses replicated in the mini-organs.
As a next step, the team is now determining which cells become infected (the tropism), how fast the viruses replicate (kinetics), and how the mini-organs respond to infection by measuring their immune responses. The team ultimately is planning to compare different strains of influenza viruses and species of wild birds and poultry.
This work has been presented locally at the University of Maryland College of Agriculture and Natural Resources (AGNR) cornerstone event (2023) and the UMD Virology Program meeting (2023 and 2024), regionally at the USDA Beltsville campus (2024), and nationally at the Building Research Areas in Virology (BRAVE) workshop (2024) and the American Society for Virology (ASV) annual meetings (2023 and 2024). In addition, Dr. Broadbent presented this work to members of the National Coalition for Food and Agricultural Research (NCFAR), congressional staff, and members of USDA including the USDA NIFA Director Dr. Manjit Misra (2024).
Other researchers are interested in using these mini-organs to study different avian diseases, and the team believes they are a valuable resource to the poultry research community. The team now have active collaborations with researchers at Emory University, University of Iowa, and the USDA, and have applied for three grants, with one successfully funded (NIH R01), where Dr. Broadbent is the co-investigator (2024).
“The work conducted during this project will help us to reduce the number of live animals that are used in their research by replacing them with the mini-organs,” said Broadbent. “This is a key component of the “3Rs” of research (reduction, refinement, and replacement).”
For more information about this Grand Challenges project, visit: https://research.umd.edu/aiv