Feline enteric corona virus

The importance of FECV as a primary intestinal pathogen is minimal. However, FECV commonly mutates in vivo and at least one mutant form ie, biotype causes a highly fatal disease known as feline infectious peritonitis FIP Poland et al. The precise nature of the mutation that causes this change in virulence has been variably ascribed to differences in the spike protein Rottier et al or to non-synonymous or deletion mutations in the 3c small envelope gene Vennema et al This altered tropism allows the virus to become a systemic pathogen of macrophages, and the resultant disease involves a complex interaction between host cellular and humoral immunity and infected macrophages Pedersen and Boyle, , Pedersen, Experimentation with FECV has been hampered by its lack of growth in tissue culture.

Therefore, infection studies have often relied on extracts of feces from cats infected with cat-to-cat passed virus Pedersen et al. Although one report suggests that a cultured strain of FCoV, WSU, is a prototypic FECV Pedersen et al b , this author now believes it to be a tissue culture attenuated recombinant of canine and feline coronavirus. This is given support by the complex patterns of recombination that have been described for WSU a highly virulent FIPV and WSU, which were both isolated from the same laboratory at the same time Herrewegh et al The present study was designed initially to prove that resistance and susceptibility to FECV infection were under genetic control, just as genetics appears to play an important role in FIPV resistance Foley et al a.

Young cats were infected with the RM strain of FECV and their patterns of fecal virus shedding quantified over extended periods of time by periodic sampling. Cats that stopped shedding the virus after 8—12 months were than bred to cats with a similar profile, and cats that appeared to be long-term shedders were bred to chronic shedders.

Their kittens were then infected with FECV at 10—23 weeks of age and the cycle continued. The goal was to create two bloodlines, one resistant and one susceptible. After more than 3 years, it became apparent that FECV resistance and susceptibility may not be definable by simple Mendelian genetics.

Therefore, a decision was made to concentrate on what was learned about FECV pathogenesis. Males and females were not neutered for this study. Select animals were chosen for breeding during the course of the study and 22 kittens produced from these mating's added to the study over time. Cats were infected with 0. The initial group of cats was infected several days after acquisition, while kittens reared during the study were infected at 12—15 weeks of age and observed for signs of acute or chronic disease.

Cats were housed in open rooms, with no more than five animals per room. These groups remained relatively stable, except when toms or queens were transferred for breeding or queens isolated for birthing and kitten rearing. Reasonable precautions were taken to limit spread of contaminated litter by caretakers; disposable coveralls, boots, foot baths, hand washing, gloves were used. Feces were collected by inserting standard cotton tipped swabs into the rectum prior to infection and at 1 week intervals for at least 2 months, and then at 1—2 month intervals thereafter.

RNA was isolated from the swabs van der Hoek et al There was no evidence for fecal inhibitors of the RT-PCR assay used in this study; SPF cat fecal samples were always negative, but became rapidly and progressively positive after experimental infection. Slides were harvested after 24—48 h and fixed in absolute acetone. Each serum was tested at , , , and dilutions in Hank's buffered saline solution. Serum was allowed to react for 1 h, slides washed, and a dilution of rabbit anti-cat IgG Antibodies Incorporated, Davis, CA was over layered for 1 h.

Slides were than washed, stained with dilute Evan's blue dye, and cover slips mounted with glycerin:saline. Slides were read on an indirect fluorescent microscope and the titer listed as the last dilution of serum that still produced noticeable fluorescence. Thirty-three cats were infected with FECV and followed sequentially for fecal virus shedding over a period of 14—48 months Table 1. Peak virus levels tended to drop to levels of 10 6 —10 9 particles per swab in the secondary stage of infection that followed Fig 1 , Fig 2 , Fig 3.

Description of 33 cats used to study patterns of fecal FECV shedding following primary infection and in the study on the effect of methylprednisolone acetate induced stress in 18 of these animals. Typical fecal FECV shedding patterns of cats demonstrating a persistent pattern of infection. Typical fecal FECV shedding patterns of cats demonstrating an intermittant pattern of infection. Typical fecal FECV shedding patterns of cats demonstrating a self-limiting recovery pattern of infection. Three different patterns of virus shedding were noted in the secondary infection stage.

Eleven cats shed the virus continuously at greatly varying levels over an observation period of 14—24 months persistent infection Table 1 ; Fig 1. Twelve cats had brief periods of recovery, interlaced with periods of virus shedding intermittent or recurrent shedders Table 1 ; Fig 2 , and 10 cats ceased shedding at 7—18 months average Three representative cats were graphed for each of the three infection outcomes Fig 1 , Fig 2 , Fig 3.

None of the cats developed FIP. Nineteen cats were used for this study and divided into two groups of four and 15 based on their virus shedding patterns prior to reinfection. The four cats that had low or non-measurable virus shedding at the time of secondary exposure were clearly reinfected. Fecal shedding for one of these cats is illustrated in Fig 4. Figure 5 shows the mean virus shedding levels for all four of the cats that were reinfectable; the peak levels of virus shedding were as high as observed during primary infection and the duration was similar 4—7 months.

No evidence for reinfection was observed in cats that had been shedding high levels of virus at the time of secondary challenge exposure Fig 6. One-way analysis of levels of fecal FECV shedding in a group of four cats that were shedding very low or non-detectable levels of virus prior to infection.

Virus levels following reinfection were higher at all time points than they were prior to infection, but because of the small group size, only weeks 3 and 4 were significantly different. One-way analysis of levels of fecal FECV shedding in a group of 15 cats that were shedding virus at the time of their secondary challenge exposure. There was no significant change in virus shedding following reinfection.

The peak level of virus shedding during their primary phase of FECV infection was compared between groups Fig 7. Kittens shed significantly higher peak levels of virus than cats 2—8 years of age; virus shedding was also higher than for aged cats, but this difference was not significant. Aged cats 8—13 years of age also tended to shed higher levels than 2—8 year olds, but the difference was also not significant. These cats were randomly selected from among the 33 animals whose infection course had been established.

However, there was considerable overlap in titers and virus shedding status among individual cats in the two groups; virus shedders and non-shedders were to be found in individuals with the lowest 5—25 and highest titers. Their fecal FECV shedding status was measured at the same time. Twenty-two kittens were born to eight different queens, and data was available for 12 of them for the first 24 weeks of their lives.

None of these 12 kittens shed FECV before 9 weeks of age, while all kittens tested at 9—11 weeks of age were shedding as a result of natural exposure Fig 9. Fecal virus shedding levels in kittens born to project queens. Kittens were infected naturally at 9—10 weeks of age, but this infection appeared transient. Kittens were experimentally infected at 10—17 weeks of age average 13 weeks.

Fecal virus shedding was measured for a period of 12 weeks before and 12 weeks after parturition in seven queens and nine litters Fig There was no significant difference in the levels of FECV shedding as a result of pregnancy, parturition or lactation. Average levels of FECV fecal shedding before and after parturition in seven queens during nine pregnancies. There was no statistical change in the levels of virus shedding post-treatment in cats given methylprednisolone acetate Fig 11 or saline data not shown.

However, a characteristic primary type infection occurred following experimental infection with FECV at 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. Abstract 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.

Close contact between cats eg, catteries and multicat households facilitates transmission. Vertical transmission from infected queens to kittens does occur. Kittens generally do not begin to shed virus before 9—10 weeks of age, although viral shedding as early as 4 weeks of age has been reported.

Soon after infection, virus may replicate in oropharyngeal tissue, resulting in transient hours to days salivary shedding. FECV infects and replicates in mature apical epithelial cells of the intestinal villi, causing brush border shortening and destruction.

Most feline enteric coronavirus infections are clinically inapparent or characterized by mild, self-limiting gastroenteritis. Occasionally, vomiting and diarrhea can be acute and severe or chronic and unresponsive to treatment.

Although diarrhea is the most common clinical sign of infection in kittens, upper respiratory tract signs have also been reported. Because chronic carriers of FECV tend to be asymptomatic, FECV can be assumed to be the cause of the diarrhea only after other causes eg, infectious, dietary, inflammatory bowel disease, neoplasia, etc have been excluded. The clinical utility of serologic evaluation for antibodies to FECV is questionable.

Positive FECV antibody titers are indicative only of exposure to the virus and are not suggestive of the etiology of the current disease, do not correlate with the risk of developing FIP, and are not diagnostic for FIP. Histologic lesions suggestive of FECV enteritis include intestinal villous fusion, atrophy, or sloughing.

Because these lesions are nonspecific, definitive diagnosis requires immunohistochemical or immunofluorescent detection of viral antigen in intestinal epithelial cells. The mild, transient clinical signs of feline enteric coronavirus are unlikely to require therapy.

Treatment, if required, is symptomatic and supportive ie, fluid therapy, oral electrolyte solutions, antiemetics. There is no specific antiviral therapy. Death due to the FECV-associated gastroenteritis is uncommon.

The virus is shed in the feces by many seropositive cats; in catteries it is a cause of inapparent to mildly severe enteritis in kittens 6 to 12 weeks of age. The virus may produce a more severe enteritis in young specific-pathogen-free kittens. Feline enteric coronavirus selectively infects the apical columnar epithelium of the intestinal villi, from the caudal part of the duodenum to the cecum. In severe infections, there are sloughing of the tips of the villi and villous atrophy.