Biology of Feline Coronavirus and Its Control
World Small Animal Veterinary Association World Congress Proceedings, 2003
Hans Lutz, Dr. med. vet.
Clinical Laboratory, Veterinary Faculty, University of Zurich
Zurich, Switzerland

Feline infectious peritonitis (FIP) was first described in the sixties of the last century. Today, it is probably the most important infectious disease of the cat. The causative agent was found to belong to the coronaviruses [1]. Between 5 and 12 % of all cats seropositive for feline coronavirus (FCoV) succumb to FIP during the first 12 months of their lives [2,3]. The biology of FIP is poorly understood and so far prevention has shown to be difficult. FIP occurs sporadically in FCoV seropositive cats and preferentially in animals originating from multiple cat households. About 75% of all FIP cases are seen in cats below 4 years and around 50% below 2 years of age [4]. FIP presents itself as a polyserositis; in a so-called dry or a effusive form. FIP is usually manifested by a therapy-resistant fever which may last for up to several weeks. In the effusive form large amounts of protein-rich fluid are found in the peritoneal or pleural cavities. In the noneffusive form surface-oriented inflammatory lesions are seen. The lesions seen in organs of FIP cases are considered to be immune-mediated. However, the pathogenesis is still unclear. Diagnosis of FIP is sometimes difficult. Abnormal findings that are typical for FIP include anorexia, unresponsive fever, lethargy, weight loss, a history of stress, anemia, neutrophilia with left-shift, lymphopenia, hypoalbuminemia, hypergammaglobulinemia, increased AST (not ALT as mentioned in earlier reports) and increased anti-FCoV antibody titers [4]. Determination of anti FCoV antibody titers is only useful in conjunction with the other parameters mentioned above and must never be used as the only criterium for diagnosis of clinical FIP. RT-PCR tests for the detection of FCoV-specific RNA are of no diagnostic use as many healthy cats are positive for FCoV, too. Almost no cat recovers from FIP once the disease has been diagnosed.

The coronaviruses which are widespread in the cat population are mostly harmless. After infection they may occasionally cause transient diarrhea and/or upper respiratory disease, but typically do not cause any clinical signs at all in spite of being present in very high concentrations not only in the intestine but more importantly in several organs including liver, spleen, kidney, lung and bone marrow [5]. Today it has become clear that FCoV usually cause chronic or at least long lasting infections which hardly can be cleared completely by the cat's immune system. In FCoV infection, there is no sterilizing immunity. However, the immune system can control the extent of viral load mostly through the cellular immunity. The humoral arm of the immune system is most likely less important for protection [6]. In contrast, antibody titers rather seem to reflect the viral load found in an infected cat [7].

Two types of FCoV are known that can be distinguished serologically and based on the nucleotide sequence of the spike protein gene: Type 1 viruses are most prevalent in European and US cats; they cannot be grown in cell culture. Type 1 viruses probably represent "prototype" feline coronaviruses. In contrast, type 2 viruses are known to be the product of recombination between canine and feline coronaviruses [8]. It is believed that type 2 viruses can originate de novo when dogs and cats with their coronavirus infections are living in close contact. Type 2 viruses can readily be isolated in cell culture. Persistently infected, healthy cats play the most important epidemiologic role in FIP, because by harbouring FcoVs in their intestines and blood, they act as a constant source of infection. Today, the amount and frequency of FCoV shed in feces can readily be quantitated by real-time PCR [7]. The shedding pattern of FCoV in cattery cats is a continuum: while few cats hardly every shed, the majority of cats shed low to intermediate amounts and few individual cats have very large amounts of FCoV in their feces. The difference of concentration between low and very high shedders may be as high as a factor of 1 million. Generally, young kittens shed the highest amounts while older cats shed significantly lower concentrations of FCoV. If one or more "high shedders" are living in a group of cats, the air, food containers and especially litter boxes will be heavily contaminated with FCoV. As transmission is via the fecal-oral route, it becomes clear that the viral load in an individual cat may be affected by the infectious pressure that exists in a group of cats living under crowded conditions.

The genesis of FIP causing viruses (so-called FIPVs) can be explained as follows: A FIPV may develop de novo from any originally harmless FCoV especially in cats with high viral loads. The RNA polymerase of coronaviruses is a "sloppy" enzyme in that it introduces 1 wrong nucleotide per 10'000 bases of newly synthesized viral RNA. As the genome of coronaviruses is 30 kilobases long, during every round of replication, 3 mutations will be introduced. In cats with very high viral loads the probability is high that some mutations occur that lead to changes of the antigenic make up (antigenic drift) or to an increase of virulence-or both. Consistent with this concept are the observations that young cats and cats in a state of immune suppression are especially prone for development of FIP. Immune suppression may be induced e.g., by FeLV infection. In earlier times when FeLV infection was widespread, FIP was predominantly seen in FeLV positive cats. Stress e.g., induced by the introduction of a kitten to a new owner is another factor leading to immune suppression. This probably explains the frequently observed FIP cases seen in kittens 2-4 months after being transferred to a new owner-even if the new owner is living in a high rise building and the kitten has no contact to other cats. As a consequence of immune suppression control over the viral load is lost and with the growth of the viral load the probability for the introduction of mutations increases.

From these observations some conclusions can be drawn that should allow to formulate some rules to keep low the risk of developing FIP:

 While it will be almost impossible to keep a cattery free of FCoV, the FCoV load should be kept as low as possible.

 To this end, cats should be kept in small groups of two to four animals. Larger groups should be avoided. Animals of different groups must not have contact.

 Food and water containers should always be assigned to the same group of cats. This can be achieved e.g., by color codes.

 Litter boxes should be cleaned as frequently as possible. By doing this, the probability that a strong shedder serves as a source for high infectious pressure for the cat that uses the litter box after the high shedder, is lowered.

 Strong shedders can be detected by testing their shedding pattern using the TaqMan real-time PCR technique [9]. To this end, fecal swabs are collected from the rectum 4 times at weekly intervals and sent to a specialized laboratory. Testing of the 4 swabs for presence and amount of FCoV allows characterization of the shedding pattern. Although this has not experimentally been proofed, removal of a high intensity shedder from a group appears to be a logical step for lowering the infectious pressure of FCoV. Circumstantial evidence suggests that high intensity shedders will decrease their shedding intensity when kept as single cats for some time.

 Early weaning according to Addie [2]: Two weeks before birth, pregnant queens should be separated and kept in a room without contact to other cats. Strict hygienic measures should be instituted. After birth, the queen and their kittens should be kept isolated from other cats until the kittens are weaned at the age of five to six weeks. The kittens should be brought up separated from other cats until they are transferred to the new owners. According to the authors, this procedure should result in FCoV-free kittens. Although our own studies performed under similar conditions could not confirm absence of FCoV in early weaned kittens, the procedure may be beneficial for other infections. It is debatable whether or not the early weaning procedure justifies the efforts associated with it.

 Vaccination: In a double blind field study conducted in Switzerland it was clearly shown that in cats vaccinated with an attenuated life FCoV vaccine significantly less FIP cases were observed than in the placebo vaccinated control group [3]. However, efficacy of the vaccine was only seen in cats that had not been infected with FCoV or that had a very low FCoV antibody titer at the time of vaccination. In view of the fact that the vast majority of kittens are seropositive at the age of 16 weeks, the time of the first vaccination, vaccination comes too late for most cats. However, as no negative side-effects were observed in vaccinated cats, vaccination can be offered to those owners that want to do everything possible to avoid FIP in their cat.

References

1.  Pedersen, N.C. Morphologic and physical characteristics of feline infectious peritonitis virus and its growth in autochthonous peritoneal cell cultures. Am J Vet Res 1976, 37(5), 567-572.

2.  Addie, D.D. & Jarrett, O. A study of naturally occurring feline coronavirus infections in kittens. Vet Rec 1992, 130(7), 133-137.

3.  Fehr, D., Holznagel, E., Bolla, S. et al. Placebocontrolled evaluation of a modified life virus vaccine against feline infectious peritonitis: safety and efficacy under field conditions. Vaccine 1997, 15(10), 1101-1109.

4.  Rohrer, C., Suter, P.F. & Lutz, H. Die Diagnostik der felinen infektiösen Peritonitis (FIP): retrospektive und prospektive Untersuchungen. Kleintierpraxis 1993, 6, 379381.

5.  Meli, M., Kipar, A., Müller, C. et al. High viral loads despite absence of clinical and pathological findings in cats experimentally infected with feline coronavirus (FCoV) type I and naturally FCoV-infected cats. Vet. Immunol. Immunopathol. in press 2003.

6.  Weiss, R.C. & Cox, N.R. Evaluation of immunity to feline infectious peritonitis in cats with cutaneous viralinduced delayed hypersensitivity. Vet Immunol Immunopathol 1989, 21(3-4), 293-309.

7.  Gut, M., Leutenegger, C.M., Schiller, I., Wiseman, A. & Lutz, H. Kinetics of Feline Coronavirus Infection In Breeding Catteries. submitted 2003.

8.  Vennema, H., Poland, A., Foley, J. & Pedersen, N.C. Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses. Virology 1998, 243(1), 150-157.

9.  Gut, M., Leutenegger, C.M., Huder, J.B., Pedersen, N.C. & Lutz, H. One-tube fluorogenic reverse transcriptionpolymerase chain reaction for the quantitation of feline coronaviruses. J Virol Methods 1999, 77(1), 37-46.

Speaker Information
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Hans Lutz, Dr. med. vet.
Clinical Laboratory, Veterinary Faculty, University of Zurich
Zurich, Switzerland


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