Feline infectious peritonitis is a well-known, highly fatal disease of cats worldwide. Despite its name, FIP is not directly transmissible, and may present with a wide variety of symptoms comprising two major forms of the disease; dry (granulomatous infiltration of multiple organs); and wet (polyserositis and multicavitary effusion). Either form is ultimately fatal to affected cats.
FIP is widely held to be caused by a mutated variant of feline enteric coronavirus (FECoV). While FECoV infection is ubiquitous worldwide, the prevalence of FIP is <5%. Mutations to FECoV affecting virulence and cell tropism (particularly changes to the spike protein) are known to influence the transition from latent or self-limiting FECoV infection to FIP. Despite the presence of these mutations, host immunological factors play a role in the development and outcome of FIP. In many ways, FIP is as much a product of the feline immune system as the coronaviral infection.
FIP occurs when the host immune system takes on a TH2 bias (a type of immune response) leading to immune complex production and ineffective viral killing. This is characterized by increased levels of the signaling molecule tumor necrosis factor-alpha (TNFα) and decreased interferon-gamma (IFNγ). The cell surface protein fDC-SIGN (encoded by the gene fCD209) is a receptor for coronavirus entry to feline cells. Two recent papers explore the role of Single Nucleotide Polymorphisms (SNPs) in these cytokine and viral entry genes in resistance and susceptibility to FIP. SNPs are small changes in genes that lead to changes in function and regulation.
In the first study, groups of retrovirus negative cats presented to a university were stratified into animals with FIP (confirmed by histopathology), and FECoV+ cats without FIP. A cross section of purebred and mixed-breed cats was represented. FIP+ cats were generally less that 1 year old, with the controls 1-3 years of age.
The researchers measured serum IFNγ levels in 82 FeCOV+ and 64 FIP+ cats, and then sequenced genomic DNA and performed molecular assays to identify and characterize SNPs within the IFNγ gene.
While several SNPs were identified, only one (+428C/T) was significantly associated with FIP resistance. This SNP lies in an intron and may be associated with the binding of IFNγ regulatory factors. Cats with this mutation were significantly less likely to be affected by FIP, and also had significantly higher serum IFNγ levels (cats without this mutation had undetectable IFNγ).
The data collected in this study suggests that identifiable changes in a specific gene (IFNg) may change a cat’s probability of getting FIP. A second paper, to be discussed later this week, continues that work. (MRK)