Clue to why cat virus turns deadly

Cat Once cats become ill with FIP, the prognosis is grave

Scientists believe they are closer to understanding why a common virus infecting cats can turn deadly.

The virus, a distant relative of the Mers and Sars coronaviruses, usually causes mild illness but in some cats the infection can be fatal.

The new findings show that the severe disease is associated with mutations in one of the viral proteins.

Details of the work have been published in the journal Emerging Infectious Diseases.

The researchers hope that their findings will lead to better diagnosis and future treatment of this killer disease.

Feline enteric coronavirus is a common infection, with anywhere between 10% and 50% of household cats being exposed to the virus. In catteries, this number is higher.

Infection is usually short-lived, but some cats can shed the virus for life - they become chronic carriers.

Whilst most infections cause mild or no symptoms, in around 10% of cats - most often the young - the virus becomes more virulent and a devastating condition called Feline Infectious Peritonitis or FIP develops - and this doesn't bode well.

Two forms of FIP occur. In the "wet" or "effusive" form, the cat's abdomen and chest fill with a viscous yellow fluid, whilst in the "dry" form it causes lesions that can affect multiple organs.

As Steve Dunham, associate professor of veterinary virology at Nottingham University, told the BBC: "From a clinical perspective, it's not a nice disease to deal with as the prognosis, once cats become ill with FIP, is grave."

The outcome is usually fatal.

Turning sinister

Why a usually benign virus infection can morph into something far more insidious has mystified scientists for years and two general theories have emerged.

The "internal mutation theory" contends that more pathogenic viruses emerge through mutation within an infected cat and these more virulent viruses spread through the body.

The alternative and less widely accepted "circulating high virulent-low virulent theory" argues that both forms of virus exist in the cat population at large and disease outcome depends on the strain of virus each cat becomes infected with.

Histology figure - canine coronavirus Here, a canine form of the coronavirus is shown infecting intestinal cells

Prof Gary Whittaker at Cornell University College of Veterinary Medicine favoured the internal mutation theory.

Previous genetic studies had failed to reveal a possible cause for the emergence of FIP but these had focused on parts of the virus that were easy to analyse.

"Some parts of the virus genome are stable and fairly easy to generate data… but these studies were limited; they weren't really able to see what was going on," explained Prof Whittaker.

"So what we did was take a slightly different approach. I'm a biochemist by training and so looked at this from a biochemical point of view: what do we know about viruses in general? Are there specific functions that we can focus down on and maybe we can see what's going on? So that's what we did."

Cleavage is key

And the function the team focused on was how the virus gains entry into a cell. To do this, the virus binds to specific receptors - doorways into the cell - and in the case of coronaviruses they use their surface spike or S protein to unlock this door.

The researchers analysed the S gene sequences of virus present in tissues obtained from cats with FIP and compared them to viral sequences in cats without it.

The results were striking. All of the viral S gene sequences from the cats without FIP contained instructions for proteins that should be broken down - or cleaved - by another protein called furin. But the sequences from cats with FIP contained mutations in this critical region.

"We were very surprised to see it there in the first place, so it was the loss of something that shouldn't be there in the first place [that was associated with FIP]," Prof Whittaker told BBC News.

And the researchers think that it is these sporadic mutations that allow the virus to spread through the cat and cause this devastating illness.

The next focus for the researchers will be to see what is happening inside infected cats in the hope that this understanding will lead to the development of future treatments.

In the meantime, the scientist hopes that their new findings will lead to development of better tests to diagnose FIP.

Dr Dunham thinks a specific test for the serious form of infection would be a significant help to veterinarians: "Any advance in our understanding of the disease which could lead to a new diagnostic test would be great.

"There is not a definitive test at the moment - other than post-mortem examination."

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