Pathogenesis of feline enteric coronavirus infection.

Fifty-one specific pathogen-free (SPF) cats 10 weeks to 13 years of age were infected with a cat-to-cat fecal-oral passed strain of feline enteric coronavirus (FECV). Clinical signs ranged from unapparent to a mild and self-limiting diarrhea. Twenty-nine of these cats were FECV naïve before infection and followed sequentially for fecal virus shedding and antibody responses over a period of 8-48 months. Fecal shedding, as determined by real-time polymerase chain reaction (RT-PCR) from rectal swabs, appeared within a week and was significantly higher in kittens than older cats. FECV shedding remained at high levels for 2-10 months before eventually evolving into one of three excretion patterns. Eleven cats shed the virus persistently at varying levels over an observation period of 9-24 months. Eleven cats appeared to have periods of virus shedding interlaced with periods of non-shedding (intermittent or recurrent shedders), and seven cats ceased shedding after 5-19 months (average 12 months). There was no change in the patterns of virus shedding among cats that were excreting FECV at the time of a secondary challenge exposure. Four cats, which had ceased shedding, re-manifested a primary type infection when secondarily infected. Cats with higher feline coronavirus (FCoV) antibody titers were significantly more likely to shed virus, while cats with lower titers were significantly less likely to be shedding. Twenty-two kittens born to experimentally infected project queens began shedding virus spontaneously, but never before 9-10 weeks of age. Natural kittenhood infections appeared to be low grade and abortive. However, a characteristic primary type infection occurred following experimental infection with FECV at 12-15 weeks of age. Pregnancy, parturition and lactation had no influence on fecal shedding by queens. Methylprednisolone acetate treatment did not induce non-shedders to shed and shedders to increase shedding

Genetic susceptibility to feline infectious peritonitis in Birman cats.

Genetic factors are presumed to influence the incidence of feline infectious peritonitis (FIP), especially among pedigreed cats. However, proof for the existence of such factors has been limited and mainly anecdotal. Therefore, we sought evidence for genetic susceptibility to FIP using feline high density single nucleotide polymorphism (SNP) arrays in a genome-wide association study (GWAS). Birman cats were chosen for GWAS because they are highly inbred and suffer a high incidence of FIP. DNA from 38 Birman cats that died of FIP and 161 healthy cats from breeders in Denmark and USA were selected for genotyping using 63K SNPs distributed across the feline genome. Danish and American Birman cats were closely related and the populations were therefore combined and analyzed in two manners: (1) all cases (FIP) vs. all controls (healthy) regardless of age, and (2) cases 1½ years of age and younger (most susceptible) vs. controls 2 years of age and older (most resistant). GWAS of the second cohort was most productive in identifying significant genome-wide associations between case and control cats. Four peaks of association with FIP susceptibility were identified, with two being identified on both analyses. Five candidate genes ELMO1, RRAGA, TNFSF10, ERAP1 and ERAP2, all relevant to what is known about FIP virus pathogenesis, were identified but no single association was fully concordant with the disease phenotype. Difficulties in doing GWAS in cats and interrogating complex genetic traits were discussed

A splice variant in KRT71 is associated with curly coat phenotype of Selkirk Rex cats.

One of the salient features of the domestic cat is the aesthetics of its fur. The Selkirk Rex breed is defined by an autosomal dominant woolly rexoid hair (ADWH) abnormality that is characterized by tightly curled hair shafts. A genome-wide case - control association study was conducted using 9 curly coated Selkirk Rex and 29 controls, including straight-coated Selkirk Rex, British Shorthair and Persian, to localize the Selkirk autosomal dominant rexoid locus (SADRE). Although the control cats were from different breed lineages, they share recent breeding histories and were validated as controls by Bayesian clustering, multi-dimensional scaling and genomic inflation. A significant association was found on cat chromosome B4 (Praw = 2.87 × 10(-11)), and a unique haplotype spanning ~600 Kb was found in all the curly coated cats. Direct sequencing of four candidate genes revealed a splice site variant within the KRT71 gene associated with the hair abnormality in Selkirk Rex

Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection

AbstractA previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4–12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity