Study: genetic detective work uncovers deadly cat virus trigger

Cats carrying the benign form of the feline coronavirus live in constant danger: at any point the virus could flip, switching to the deadly form with fatal and gruesome consequences for the cat.

The deadly form has one of two effects for the cat: it can cause an immune response that forces fluid to leak from the cat's blood and accumulate in the cat's stomach cavity; or it infects the cat's brain and central nervous system, resulting in neurological damage. Both options result in the cat's death and there is no cure.

But now, in a feat of detective work worthy of Colombo, a team from the Cornell University College of Veterinary Medicine, New York, has identified the mechanism that causes the virus to turn deadly, a discovery that may help efforts to diagnose and one day treat cats with the feline coronavirus.

A coronavirus is a fairly common type of virus, named for its crown-like appearance. The feline coronavirus is a distant relative of the Mers human coronavirus. Feline enteric coronavirus (FECV) is the benign form, while feline infectious peritonitis virus (FIPV) is its deadly counterpart.

"The two are [nearly] indistinguishable from a genetic point of view," says Gary Whittaker, co-author of the study published in the July issue of Emerging Infectious Diseases. But the few genetic differences they do have are the difference between life and death.

Searching for the genetic switch that turns the feline coronavirus deadly was like "searching for a needle in a haystack" says Whittaker, and required a fair amount of genetic sleuthing.
The team first looked at a better known virus, the influenza virus, and applied the knowledge about the active areas of its genome to the feline coronavirus. In essence, they started their coronavirus hunt in the same place in the genetic code as some of the important mechanisms of the influenza virus.

They sourced benign and deadly samples of the coronavirus and began to compare them. By repeatedly examining the same area of the genome in different samples of benign virus, and then in different samples of deadly virus, they were hoping to spot the telltale signs that would giveaway the virus' secret.


Eventually, they spotted something. A block of six amino acids in the benign virus -- despite being surrounded by highly variable parts of the genome -- were unchanging. From one sample of the benign virus to the next, this particular area was very well conserved.

The smoking gun came when they looked at the same area of the deadly virus and found mutations. When the virus switched to its deadly form, this block of amino acids changed. Bingo.
Typically, the benign version of the virus resides in the gastrointestinal tract of the cat, whereas the deadly form spreads throughout the cat's body by infecting macrophages, which are immune system cells.
The mutation in the six amino acids allows the virus to access the macrophages, says Whittaker. It has the effect of "changing a key which fits into the door for the gastrointestinal tract into a key which fits into the door of macrophages in the cat's bodies," he explains.

The benign form of the coronavirus is thought to be fairly common, with one Japanese study suggesting that around two thirds of cats carry it. Around one to five percent of those cases will flip into the deadly form, with cats residing in high-density locations, like shelters, particularly at risk.
Whittaker says understanding the virus better could help us better diagnose the presence of the deadly form but also to understand cat physiology better.

He points out that while dogs have a canine form of the coronavirus, they don't experience the same deadly effects as cats: "there's something about the cat's immune system" that makes it susceptible, he notes.

Which suggests, in this case at least, that dogs really are better than cats.