Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene

Abstract

Feline infectious peritonitis (FIP) is an immune-mediated, highly lethal disease caused by feline coronavirus (FCoV) infection. Currently, no protective vaccine or effective treatment for the disease is available. Studies have found that some cats survive the challenge of virulent FCoV isolates. Since cellular immunity is thought to be critical in preventing FIP and because diseased cats often show a significant decrease in interferon-γ (IFN-γ) production, we investigated whether single nucleotide polymorphisms (SNP) in the feline IFN-γ gene (fIFNG) are associated with the outcome of infection. A total of 82 asymptomatic and 63 FIP cats were analyzed, and 16 SNP were identified in intron 1 of fIFNG. Among these SNP, the fFING + 428 T allele was shown to be a FIP-resistant allele (p = 0.03), and the heterozygous genotypes 01C/T and +408C/T were found to be FIP-susceptible factors (p = 0.004). Furthermore, an fIFNG + 428 resistant allele also showed a clear correlation with the plasma level of IFN-γ in FIP cats. For the identification of these three FIP-related SNP, genotyping methods were established using amplification refractory mutation system PCR (ARMS-PCR) and restriction fragment length polymorphisms (RFLP), and the different genotypes could easily be identified without sequencing. The identification of additional FIP-related SNP will allow the selection of resistant cats and decrease the morbidity of the cat population to FIP.

Inflammatory Mediators in the Mesenteric Lymph Nodes, Site of a Possible Intermediate Phase in the Immune Response to Feline Coronavirus and the Pathogenesis of Feline Infectious Peritonitis?

“…These type I and II interferons have major antiviral roles in the innate immune system. IFN-g in particular has been of interest in FIP, as levels of this potentially protective cytokine tend to be low in the peripheral blood of diseased animals and host gene polymorphisms have been identified that may contribute to resistance against the disease (Gelain et al, 2006;Hsieh and Chueh, 2014). Similarly to the apparent lack of impact of mediator levels on the presence of lesions or effusions in FIP, this suggests that MLN IFN production has a more local effect.…”

Genetic deficiency and polymorphisms of cyclophilin A reveal its essential role for Human Coronavirus 229E replication

“…The -336AG/GG genotype was associated with lower standardized lactatedehydrogenase (LDH) levels compared with the '-336AA' genotype carrying patients with a 60% chance of having a poorer prognosis because of higher LDH levels. In cats, several SNPs have been described in CD209, TNF-a [51] and IFN-g [52] genes. They were found to be associated with the outcome of FCoV infection, that is, with the susceptibility for or the resistance to Feline Infectious Peritonitis (FIP), an immune-mediated, highly lethal disease without effective therapy and prevention.…”

Feline Coronaviruses

“…The underlying mechanism for this phenomenon is not completely understood, but it is assumed that immunosuppression favors the generation of escape mutants and thereby, the probability of clinical manifestation of FIP. Furthermore, genetic predisposition to FIP was suggested (Golovko et al, 2013;Hsieh and Chueh, 2014;Pedersen, 2009;Pesteanu-Somogyi et al, 2006;Wang et al, 2014;Worthing et al, 2012).…”