Polymorphisms in the feline TNFA and CD209 genes are associated with the outcome of feline coronavirus infection

Abstract

Feline infectious peritonitis (FIP), caused by feline coronavirus (FCoV) infection, is a highly lethal disease without effective therapy and prevention. With an immune-mediated disease entity, host genetic variant was suggested to influence the occurrence of FIP. This study aimed at evaluating cytokine-associated single nucleotide polymorphisms (SNPs), i.e., tumor necrosis factor alpha (TNF-α), receptor-associated SNPs, i.e., C-type lectin DC-SIGN (CD209), and the five FIP-associated SNPs identified from Birman cats of USA and Denmark origins and their associations with the outcome of FCoV infection in 71 FIP cats and 93 FCoV infected non-FIP cats in a genetically more diverse cat populations. A promoter variant, fTNFA - 421 T, was found to be a disease-resistance allele. One SNP was identified in the extracellular domain (ECD) of fCD209 at position +1900, a G to A substitution, and the A allele was associated with FIP susceptibility. Three SNPs located in the introns of fCD209, at positions +2276, +2392, and +2713, were identified to be associated with the outcome of FCoV infection, with statistical relevance. In contrast, among the five Birman FIP cat-associated SNPs, no genotype or allele showed significant differences between our FIP and non-FIP groups. As disease resistance is multifactorial and several other host genes could involve in the development of FIP, the five genetic traits identified in this study should facilitate in the future breeding of the disease-resistant animal to reduce the occurrence of cats succumbing to FIP.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-014-0123-6) contains supplementary material, which is available to authorized users.

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).…”

Evaluation of Interferon-Gamma Polymorphisms as a Risk Factor in Feline Infectious Peritonitis Development in Non-Pedigree Cats—A Large Cohort Study

“…Nucleotide variations within the genome (e.g., SNPs) may influence activity of the associated protein(s) by altering the translated amino-acid sequence (e.g., by missense or nonsense changes to the exonic sequence, or changes to the intronic sequence resulting in altered splicing of the transcribed messenger RNA) or by relatively increasing or decreasing the amount of the gene that is transcribed and ultimately translated into interferon-gamma (IFN-γ). Sequencing of various genes encoding inflammatory mediators have identified SNPs and their genotype variants with either increased or decreased prevalence in populations of cats with FIP, as compared to control populations [ 14 , 18 ], including SNPs in non-coding intronic regions of fIFNG [ 14 ]. This led to the suggestion that characterization of feline inflammatory mediator SNPs could be used to guide breeding of cats with increased resistance to FIP [ 18 ].…”

“…Sequencing of various genes encoding inflammatory mediators have identified SNPs and their genotype variants with either increased or decreased prevalence in populations of cats with FIP, as compared to control populations [ 14 , 18 ], including SNPs in non-coding intronic regions of fIFNG [ 14 ]. This led to the suggestion that characterization of feline inflammatory mediator SNPs could be used to guide breeding of cats with increased resistance to FIP [ 18 ]. Although our data are consistent with the previous finding of fIFNG loci g.401 and g.408 being in complete linkage disequilibrium and an association between these loci and risk of FIP, that is where the agreement ends [ 14 , 15 ].…”