Scientists clarify how the virus attacks the cat’s kidney


PITTSBURGH – In a study published this week in the Proceedings of the National Academy of SciencesVirologists at the University of Pittsburgh Vaccine Research Center reverse-engineered an elusive virus linked to chronic kidney disease in cats and described its mechanism of infection, highlighting its potential to infect people.

The research suggested that feline morbillivirus, or FeMV, uses the same cellular entry and infection mechanism as other viruses in the morbillivirus family, such as measles. Unlike measles, however, FeMV appears to spread from host to host via urine in a similar way to the zoonotic Nipah virus harbored in bats, which causes annual deadly outbreaks in humans across Southeast Asia.

The study provides the first clear insight into this little-studied virus and its potential trajectory from infecting animals to jumping to humans.

Paul Duprex“Feline morbillivirus remained under the radar for many years,” said lead author Paul Duprex, Ph.D., director of the Center for Vaccine Research at Pitt School of Medicine. “By understanding the genetics of a virus that was challenging to grow in the lab, we can now shed light on its connection to chronic kidney disease and better understand how we can stop transmission and potential spread to human populations.”

First discovered in feral cats in Hong Kong a decade ago, FeMV has since been found in domestic cats in Asia and Europe, and was fully identified and sequenced in the US by the Duprex research team in 2016. when they worked in Boston. While previous studies have linked FeMV infections to chronic kidney disease in cats, a leading cause of death in older animals, the new study shows in unprecedented detail how the virus reaches the kidneys.

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Like other members of the same viral family, FeMV enters cells by binding to a surface protein receptor called CD150. Related viruses, including measles, use CD150 as their main receptor for entry, and persons vaccinated against measles are protected against FeMV infection. However, measles eradication could present an evolutionary opportunity for other morbilliviruses, such as FeMV, to seek out new hosts and jump to unvaccinated people.

“That’s why proactively shining a light on animal diseases is important,” Duprex said. “Preparation is vital to avoid an epidemic.”

By creating a genetically engineered version of FeMV that contains a fluorescent probe, the researchers were able to track its spread through cells and organs, and found that its transmission can be stopped by inhibiting a class of protein-cleaving enzymes called cathepsins. Interestingly, cathepsins are primarily used by Nipah viruses but not by morbilliviruses, suggesting that FeMV is an evolutionary intermediate between the two viral families.

“It’s important to understand animal pathogens because they can become pathogens in people,” Duprex said. “Learning about the viruses that infect cats is not only important for reducing rates of kidney failure in our beloved pets, it also helps us understand something new about emerging infectious diseases and how they can spread between different animal species. There are about 85 million cats in the US and more than 500 million in the world. We live with them very close, and their health is important.”

Other study authors include Sham Nambulli, Ph.D., Linda Rennick, Ph.D., and Natasha Tilson-Lunel, Ph.D., all of Pitt; Andrew Acciardo, Ph.D., Gregory Ho, Ph.D., Nicholas Crossland, Ph.D., and Kathy Hardcastle, Ph.D., all from Boston University; Betsy Nieto, B.Sc., Graeme Bainbridge, Ph.D. and Tracey Williams, B.Sc., all of Zoetis, Kalamazoo, Mich.; and Claire Sharp, Ph.D., of Murdoch University, Australia.

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This research was supported by Zoetis and the University of Pittsburgh.

PHOTO DETAILS: (click images for high resolution versions)

CREDIT: Joshua Franzos, courtesy of the Pittsburgh Foundation

CAPTION: Paul Duprex, Ph.D.

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