by Carly Hodes, Cornell University
Jun. 24, 2013 (TSR) – Scientists have uncovered the mutation that transforms a harmless virus into what is the most lethal infectious disease in cats.
The finding is expected to open the door to the development of the first working diagnostics, vaccines, and treatments for the disease, feline infectious peritonitis (FIP).
FIP develops when feline enteric coronavirus (FECV), a common benign intestinal virus, mutates into the malignant FIPV virus.
Discovered in 1963, this mutant moves from intestinal cells to white blood cells called macrophages. Traveling through the body, it kills most cats within weeks. Kittens are particularly vulnerable, especially in shelters and catteries. Current tests cannot distinguish between the common FECV and the killer FIPV. There are no effective vaccines or therapies.
“FIP is a tragic disease for families falling in love with new kittens and for veterinarians who can do nothing to stop it,” says Gary Whittaker, virology professor at Cornell University’s College of Veterinary Medicine.
“Comparing viral genetics, our lab found exactly what changes when FECV mutates into FIPV. This knowledge will prove pivotal in developing tests, vaccines and treatments to protect cats from this devastating disease.”
As reported in the journal Emerging Infectious Disease, scientists have searched for the mutation for the last three decades. Part of the challenge, might have been the scale at which they searched. Like flu viruses, coronaviruses code genes with RNA. RNA-based viruses make many mistakes when replicating, allowing them to quickly mutate, dodge vaccines and therapeutics, and move to new territory.
“These viruses are so rife with mutations that even samples of the same virus from the same tissue in the same cat rarely match to the letter,” says Whittaker. “Sifting through for something that distinguishes FIPV was like looking for a needle in a haystack.”
So Whittaker deviated from taking the traditional birds-eye view, focusing instead on a specific functional part of the virus.
Coronavirus particles brim with crowns of spikey proteins that activate the virus when chopped by the right proteases—ax -like enzymes in the host cell. FECV prefers proteases from its main ride, intestinal cells. When FIPV hijacks macrophages instead, Whittaker suspected its spike proteins have changed shape to respond to macrophage proteases.
Using biochemical analysis and traditional comparative genomic analysis, scientists focused on the area where proteases cut spike proteins and amassed an unprecedented collection of feline coronavirus, gathering hundreds of samples donated from pet owners, veterinarians and—with help from pathology professor Gerald Duhamel—Cornell’s pathology vault.
Comparing the spot in quiet FECV to the same spot in killer FIPV, they found a distinct set of differences in the spike proteins and the genes that code them. This set of mutations matched FIPV’s behavioral change and appeared across samples with consistency unparalleled in the quest for the mutation.
“Using a unique interdisciplinary approach, we’ve found the first known molecular basis for FIP,” Whittaker says.
“This could have implications for similar coronaviruses, such as FIPV’s deadly cousin in ferrets and another human-infecting cousin emerging in the Middle East. For now, it finally unlocks the door to developing the world’s first effective diagnostics, preventions and therapies for FIP in cats.”
Cornell’s Feline Health Center, the Winn Feline Foundation, and the Morris Animal Foundation funded the research.