PNAS: How the virus attacks a cat's kidneys and then passes it on to humans

In a study published this week in the Proceedings of the National Academy of Sciences, virologists at the University of Pittsburgh's Vaccine Research Center reverseengineered an elusive virus linked to chronic kidney disease in cats and described its infection mechanism, outlining its potential to
infect humans.

Studies have shown that feline measles virus (FeMV) uses the same cellular entry and infection mechanisms
as other viruses in the measles virus family, such as measles.
However, unlike measles, FeMV appears to be transmitted from host to host in urine, in a manner similar to the bido Nipah virus in bats, which causes deadly outbreaks
in humans in Southeast Asia every year.

The study is the first to provide a clear picture of this understudied virus and its potential trajectory
from infecting animals to infecting humans.

Senior author Paul Duprex, director of the Vaccine Research Center at Pitt Medical School, said: "The feline measles virus has gone unnoticed
for many years.
"By understanding the genes of a challenging virus grown in the lab, we are now able to uncover its link to chronic kidney disease and better understand how we can stop transmission and potential spillover into human populations
.
"

FeMV was first discovered in stray cats in Hong Kong 10 years ago, has since been found in domestic cats in Asia and Europe, and was discovered and fully sequenced
in the United States in 2016 while Duprex's research team was working in Boston.
Previous studies have linked FeMV infection to chronic kidney disease in cats, one of the leading causes of death in older animals, and the new study shows in unprecedented detail how the virus reaches the kidneys
.

Similar to other members of the same viral family, FeMV enters cells
by binding to a surface protein receptor called CD150.
Related viruses, including measles viruses, use CD150 as their primary entry receptor, and people vaccinated against measles can avoid infection with FeMV.

However, measles eradication may provide an evolutionary opportunity for other measles viruses, such as FeMV, to seek new hosts and infect unvaccinated people
.

"That's why it's important
to actively reveal animal diseases," Duprex said.
"Preparedness is essential
to stop epidemics.
"

By making a transgenic FeMV containing a fluorescent probe, the researchers were able to track its spread through cells and organs, and found that its spread could be stopped
by inhibiting a protein-splitting enzyme called cathepsin.
Interestingly, cathepsins are mainly used by Nipah virus, not Malibi virus, suggesting that FeMV is an evolutionary
intermediate between the two viral families.

"It's important to understand the pathogens of animals because they can become pathogens
for humans," Duprex said.
"Understanding the virus that infects cats is not only important to reduce the rate of kidney failure in our beloved pets, but also helps us understand emerging infectious diseases and how they spread between different animal species
.
There are about 85 million cats in the United States and more than 500 million in the world
.
We live close to them and their health is important
.
”

Other authors of the study include Dr.
Sham Nembley, Dr.
Linda Rennick, and Dr.
Natasha Tilson-Rounier, all from Pitt University; Dr.
Andrew Acciardo, Dr.
Gregory Ho, Dr.
Nicholas Crossland, and Dr.
Kathy Hardcastle, all Boston University; Betsy Nieto, B.
S.
, Graeme Bainbridge, Ph.
D.
, Tracy Williams, B.
S.
, Zotis, Kalamazoo, Michigan; and Dr.

Claire Sharp of Murdoch University, Australia.

The study was supported
by Zoetis and the University of Pittsburgh.