UMN CVM scientists unlock decades-old mystery in epidemiology

December 27, 2019

 A team of researchers led by Fang Li, PhD, associate professor in the Department of Veterinary and Biomedical Sciences (VBS) at the University of Minnesota (UMN) College of Veterinary Medicine (CVM), published a paper earlier this month that could pave the way for more-effective vaccination and therapeutic approaches for combating coronaviruses.

Antibody-dependent enhancement (ADE), a phenomenon where antibodies facilitate a viral infection rather than fighting it, has eluded epidemiologists for decades. Until now, scientists did not fully understand how ADE was taking place. When people become infected by certain viruses, ADE can exacerbate the infection and turn a mild ailment into a life-threatening situation.

“Some cells have viral receptors, which allow viruses to infect these cells and help viral infection to spread. Antibodies can block viral infection by binding to the viruses and effectively keeping the viruses away from these cells,” says Li. “Meanwhile, some cells have antibody receptors, which allow antibodies to enter these cells.” Li’s team found that the antibodies can facilitate coronavirus infections by bringing viruses into cells that express antibody receptors. In other words, antibodies and antibody receptors together mimic the functions of viral receptors. To make things worse, these cells that express antibody receptors are often immune cells and travel around the body in the bloodstream, potentially disseminating viruses to the whole body.

This team of scientists also found that certain concentrations of antibodies can be used in antibody-based drug therapies to treat infection without causing ADE. Next, they plan to measure which concentrations of antibodies are associated with setting off an ADE reaction in the body.

This novel research could directly impact vaccine and antibody therapies developed for combating coronavirus infections in both humans and animals alike. This includes Middle East respiratory syndrome coronavirus (commonly referred to as MERS), severe acute respiratory syndrome (commonly referred to as SARS) and porcine epidemic diarrhea virus (commonly referred to as PED), which takes a toll on the swine production industry. This research could also help scientists understand other types of viruses.

“ADE used to be such a mysterious process,” says Li. “But we have found that it is actually a fairly straightforward process. It’s a very clear and simple mechanism.”

The scientists are also interested in applying this research to feline infectious peritonitis coronavirus (FIPV), which is a leading cause of death in kittens and young cats and is most common in indoor, multicat environments, such as shelters and catteries. FIPV usually strikes kittens and is almost always fatal.

The research was recently published online in the Journal of Virology. Yushun Wan, PhD, and Jian Shang, PhD, two postdoctoral fellows in Li’s group, are the lead authors of the paper. Collaborators include scientists from New York Blood Center, Beijing Institute of Microbiology and Epidemiology, and Chinese Academy of Sciences. Jianming Wu, DVM, PhD, associate professor in VBS and a leading researcher on antibody receptors, also contributed to the study. The research is funded by three National Institutes of Health R01 grants awarded to Li and his collaborators.

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CONTACT

Fang Li, lifang@umn.edu, 612-625-6149