November 28, 2016
Researchers from the University of North Carolina at Chapel Hill have published a new mouse model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. This publication marks the first time that an animal model has successfully reproduced the MERS-CoV disease symptoms seen in human patients.
“This is a significant development to control the deadly MERS-CoV,” said Ralph S. Baric, PhD, professor of epidemiology at the UNC Gillings School of Global Public Health and a senior author of the manuscript. “Animal models that faithfully recapitulate the human disease spectrum are more likely to identify drugs and vaccines that will work in humans.”
MERS-CoV, which causes acute respiratory distress syndrome (ARDS), can lead to severe pneumonia-like symptoms and multi-organ failure. In humans, the virus has a case fatality rate of about 36 percent. Since it emerged in 2012, researchers have struggled to duplicate the symptoms of late-stage ARDS in animal models.
Such modeling usually provides a path to better understanding a disease and identifying possible cures, but the small animals typically used in such studies – mice, hamsters, guinea-pigs and ferrets – are naturally resistant to MERS-CoV.
Now, a team of researchers has modified the mouse genome and created a mouse-adapted virus. The full article on this process, titled “A mouse model for MERS coronavirus-induced acute respiratory distress syndrome,” was published online Nov. 28 by Nature Microbiology.
“Developing a robust mouse model for MERS-CoV required that we first identify the key residues between the mouse and human receptor that prevent MERS-CoV growth in mice,” said lead author Adam S. Cockrell, PhD, research associate in the Department of Epidemiology at the Gillings School. “Then, we used gene-editing tools to introduce two human mutations into the mouse genome, generating a mouse that was highly susceptible to MERS-CoV.”
Cockrell also noted other possible applications of the researchers’ process: “This approach can be applied to many emerging, highly pathogenic human viruses which don’t replicate in mice. It could lead to improved mouse models for high-throughput evaluation of vaccines and therapeutics, as well as improve our understanding of precisely how these dangerous viruses cause disease.”
Once the researchers had developed a mouse population that exhibited symptoms indicative of severe ARDS, they were able to test therapeutic countermeasures including a MERS-CoV neutralizing antibody treatment and a MERS-CoV spike protein vaccine. Importantly, both approaches protected the engineered mice against MERS coronavirus-induced ARDS, offering hope against the potential of a future pandemic.
“This is the first time that genome-editing tools have been applied to genetically modify virus host susceptibility in a species, leading to new strategies to combat emerging viruses,” Baric said. “Hopefully, this will also lead to improved global health. The implications for public health preparedness are enormous.”
Additional co-authors from the Gillings School include Boyd L. Yount, research specialist, Trevor Scobey, laboratory technician, Kara Jensen, PhD, postdoctoral research associate, Madeline Douglas, undergraduate student researcher, and Anne Beall, graduate student, all in the Department of Epidemiology.