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Molecular basis of feline coronavirus pathogenesis

Licitra BN, Millet JK, Regan AD, et al. Mutation in spike protein cleavage site and pathogenesis of feline coronavirus. Emerg Infect Dis. 2013; 19: 1066-73. [Free, full text article]

Feline infectious peritonitis (FIP) remains a frustrating disease for veterinarians and a heartbreaking diagnosis for cat owners. The pathogenesis of this disease is the subject of much research, including this study partly funded by the Winn Feline Foundation. The exciting results from these investigators may herald major progress in unraveling the FIP mystery.

The focus of this research was a small area of an important viral protein, the spike protein. As the name indicates, this protein protrudes from the virus and functions in the virus replication. As part of this viral replication, the spike protein is believed to be cleaved into two pieces, an important step in successful infection of the cell. These researchers speculated that the site of this cleavage was an important feature of the virus, and mutations of this site would lead to the virus’ ability to cause the lethal disease. 

To explore this possibility, the investigators analyzed this region in viruses from cases of FIP as well as from virus in asymptomatic healthy cats. They found that while the enteric, harmless form of the viruses all shared the same genetic sequence at this site, mutations in this region occurred in the majority of viruses from FIP cases. These mutations are believed to lead to a change in the virus that allows it to target a cell type important in the cat’s immune system rather than the intestinal cells that the harmless virus targets. This change leads to the production of the lesions associated with FIP. 
While still in the early stages of analysis, this discovery could lead to improved diagnostics as well as treatment for FIP. [MK]

Funding: This project was partly funded by Winn/Miller Trust grant MT08-004.

Winn is seeking sponsors for our current FIP project:
W13-020 : In vivo efficacy study of virus protease inhibitors against feline coronaviruses in a mouse model; $19,920
Yunjeong Kim; Kansas State University
Despite the importance of FIP as the leading infectious cause of death in young cats, there is no specific treatment approved for FIP. Therefore, it is highly desirable to develop antiviral drugs for FIP to prolong the length and quality of life for cats affected by this devastating disease. The feline coronavirus uses protease enzymes for virus replication. These researchers recently discovered novel inhibitors against the feline coronavirus 3CL protease, and these inhibitors potently inhibited the replication of feline coronaviruses in cells. The goal of this project is to test the antiviral activity of protease inhibitors in a mouse model.

See also: Rottier PJ, Nakamura K, Schellen P, Volders H and Haijema BJ. Acquisition of macrophage tropism during the pathogenesis of feline infectious peritonitis is determined by mutations in the feline coronavirus spike protein. J Virol. 2005; 79: 14122-30. [Free, full text article]