Study proves transmission of feline coronavirus between domestic and wild cats

A new study by researchers at the College of Veterinary Medicine reveals the first genetic evidence of feline coronavirus (FCoV) transmission between a captive wild cat and a domestic cat.

This discovery, made possible by a new approach using next-generation sequencing by hybridization-capture, has implications for the fight against this little-known virus and its consequences, as well as against other diseases.

“We don’t know exactly what FCoV is capable of and how it’s transmitted,” said Gary Whittaker, the James Law Professor of Virology in the departments of Microbiology and Immunology and Public and Ecosystem Health, and corresponding author of the paper, which was published in Spectrum of microbiology.

The paper’s first author is Ximena Olarte Castillo, a postdoctoral associate in the lab of co-author Laura Goodman, Ph.D. ’07, assistant professor in the Department of Ecosystem and Public Health and the Baker Institute for Animal Health.

Previous research has identified two distinct genotypes of FCoV, called types 1 and 2. They differ in their viral spike (S) protein, which determines the types of cells the virus can infect. Current evidence suggests that certain mutations in either version of FCoV may allow certain subtypes to attack different types of cells and transform the virus from a low-pathogenic form to a highly pathogenic form.

Although FCoV typically causes only mild symptoms and can be present for years without causing problems in most domestic cats, some strains mutate and cause feline infectious peritonitis (FIP).

First described by Dr. Jean Holzworth, DVM ’50 in 1963, FIP frequently causes systemic and neurologic signs and was considered almost always fatal until the relatively recent development of safe and effective antiviral drugs (the most effective being a compound called GS-441524). There is currently no effective vaccine for the prevention of FIP in cats.

Since wild felines (cats) are close genetic relatives of domestic cats, they may be particularly susceptible to infection with diseases such as FCoV and, as a result, succumb to FIP. Food intended for stray cats, for example, may attract wild felines, increasing the risk of transmission.

More recently, Whittaker and other researchers characterized an ongoing outbreak of a novel FCoV-2 in feral, stray, and free-roaming cats in Cyprus, with a 40-fold increase in virus-related deaths reported on the island.

The current article reviews a case of FCoV-1 transmission between a domestic cat and a wild feline that occurred at a U.S. zoological institution in 2008. The domestic cat and a young Pallas’s cat, a species native to central and western Asia, shared a room and both died of FIP. By examining frozen tissue samples from both animals, the researchers hoped to make progress on a major mystery about feline coronaviruses.

Although FCoV has been reported in many wild felid species, the specific genotype (FCoV-1 or FCoV-2) remains unknown due to technical challenges in sequencing the highly variable S gene.

“Using a semi-targeted approach, known as hybridization capture, together with next-generation sequencing, we were able to detect and sequence the entire genome of FCoV-1 in tissues from the domestic cat and Pallas’s cat,” said Olarte Castillo. “The main differences between FCoV-1 and FCoV-2 are in highly variable regions. So we need to move from targeting specific genes to sequencing the entire genome, and this technique looks very promising.”

Although the current study is retrospective, “now that we have the technology, we realized that this sample could serve as a proof of principle for an effective response to an outbreak,” Whittaker said.

To this end, the Cornell Feline Health Center (FHC) recently provided rapid response funding for a next-generation NextSeq 1000 sequencer, housed in the Baker Institute’s laboratories.

“The FHC has made a big investment so that if there is a future outbreak, we can be ready and very quickly to determine what strain we are dealing with,” Goodman said. “We hope to be able to provide clinicians with the information they need as soon as possible to respond and contain the emerging situation.”

“This study is very important because it not only provides the first evidence of FCoV-1 transmission between a domestic cat and a wild feline, but also because it uses cutting-edge technology that can be applied to improve surveillance efforts for FCoV and other pathogens in domestic and wild feline species around the world,” said Bruce Kornreich, DVM ’92, Ph.D. ’05, director of the FHC.

In the long term, the researchers hope that their efforts to sequence FCoV – and other diseases – will help better understand the virus’s potential for drug resistance, now that antivirals are in widespread use for FIP, and determine best management practices for conservation.

“We need to gain some basic knowledge to determine what kind of management is needed in the future,” Whittaker said.