• Introduction
• Overview
• Session 1: Background to FCoV/FIP
  • Presentation 1.1: Overview and Historical Perspective on FCoV/FIP.
  • Presentation 1.2: Living with Feline Coronavirus
• Session 2: Diagnosis & Treatment of FIP
• Session 3: Epidemiology of FCoV Infection
• Session 4: Pathogenesis and Immunopathogenesis of FIP
• Session 5: Prevention of FCoV Infection/FIP
• Workshop Results
• Glossary

Session 1:
Background to FCoV/FIP
Chair, Dr. Diane Addie, University of Glasgow

Presentation 1.1:
Overview and Historical Perspective on FCoV/FIP.
Presenter: Niels Pedersen, DVM, University of California at Davis.

Dr. Niels Pedersen

Dr. Pedersen gave a comprehensive overview of feline infectious peritonitis and feline enteric coronavirus.

Historical records suggest a case of FIP was identified as early as 1954, but the disease was first described in 1963. It has received a great deal of attention from researchers since the early 1970's. The incidence of FIP increased dramatically from the 1960's onward, and is now considered to be the single leading infectious cause of mortality among pet cats. Dr. Pedersen believes that the increased incidence of FIP over the last 40 years is not due to a recent appearance of the causative virus, but rather to changes in husbandry that favor the infection. Cats have become more valued as pets and the number of cats per family has increased. In addition, many cats are kept indoors in multi-cat groups. This may have led to the increasing occurrence and recognition of FIP. The causative virus is spread by fecal-oral contact, which is minimal in outdoor environments and maximal in indoor situations.

FIP is primarily a disease of younger cats (3-36 months of age) originating from multi-cat environments, such as shelters or catteries. Unfortunately, there is no cure and more than 95% of sick cats will die. In the highest risk groups (young cats in multi-cat environments), the mortality rate is 5% - 10%. Cats in the same environment have the same strains of FECV from which develop genetically related strains of FIP virus.

Before feline leukemia virus was eliminated from catteries, there was a documented relationship between cats who had feline leukemia (FeLV) and those who had FIP. Subsequent research demonstrated that FeLV had a potent suppressive effect on FIPV immunity, thus preventing many cats from recovering. Reports of increases in the incidence of FIP in cats vaccinated against FeLV has been attributed to stress and with improved vaccines is no longer an issue.

There are at least two distinct strains (serotypes) of feline enteric coronaviruses (Type I and Type II). Type I is uniquely feline, while type II appears to be a genetic hybrid of feline and canine coronavirus. Some researchers believe that there is also a Type III. The various FIP viruses are mutants of the relatively non-pathogenic feline enteric coronavirus (FECV). The ease with which feline coronaviruses recombine with related viruses, and undergo internal mutations, make them interesting for genetic studies. FECV isolates from within a cattery in the West Coast will all be identical to each other, but genetically distinguishable from FECV isolates from unrelated cats in the East Coast. There are two different forms of FIP, the dry and wet form. The amount of virus in the macrophages (part of the immune system) is noticeably less in the dry form than in the wet form and it is believed that cats with the dry form have a partial immune response.

Recent studies have proven that the FIP virus (FIPV) is a simple mutation of FECV virus. FECV attacks the epithelial cells at the tips of the small intestinal villi during acute infection, and seems to be shed from the colon during the subsequent carrier state. FECV infection of kittens can occur as young as 3 weeks of age in catteries and between 8 and 16 weeks in nature. There is a 5-10% likelihood that an FIP producing mutation will occur. The mutation occurs mainly during the initial infection in kittens. The mutation leading to FIPV involves a deletion or insertion in the 3c gene, a gene that codes for coronavirus membrane proteins. This mutation enables the coronavirus to infect immune system cells called macrophages very easily, thus spreading the virus throughout the cat's body. There are two recognized biotypes of feline coronavirus. The FECV form infects the mature cells lining the intestinal tract and is minimally pathogenic. The FIPV form however, infects macrophages spreading throughout the body and is highly pathogenic.

Only coronavirus that is in the gut is shed in the feces, thus it is FECV and not FIPV that is generally found in fecal samples. The mutated FIP virus is rarely shed in the stool thereby greatly reducing concerns about a cat with FIP directly transmitting the disease. Each cat with FIP had to develop its own mutation from the intestinal FECV.

FECV is rarely associated with disease, other than an occasional case of transient vomiting and diarrhea. The worst diseases are associated with the mutant FIPV. FIPV infection appears as two different disease entities, dry (non-effusive) FIP or wet (effusive) FIP. Wet FIP results from a total failure of cellular immunity, while cats with dry FIP have a partial cell-mediated immune response. Humoral (antibody) immunity occurs in both wet and dry forms, but appears to be harmful rather than beneficial.

During the 1990's when the temperature sensitive intranasal FIP vaccine was introduced, there was concern that enhancement of virulence would be seen when vaccinated cats encountered field strains of virus. This was found to be a "laboratory effect" and not clinically relevant (i.e., it does not appear to contribute to the incidence or severity of FIP in nature).

The following are some of the key dates in the recognition and understanding of FIP:

FECV/FIP Timeline

• 1954: First recorded case of FIP at Angell Memorial Hospital in Boston.
• 1963: Dr. Jean Holzwoth reports the first known cases of FIP.
• 1966: The pathologists at Ohio State described the pathologic features of FIP.
• 1970's: The causative agent is identified as a coronavirus.
• 1971: First description of the disease to recognize the two forms -- wet and dry.
• 1975: Studies showed FeLV infection is a significant co-factor for FIP.
• 1976: FIP virus is grown in culture for the first time.
• 1976: First serologic test for FIP is developed by Niels Pedersen. Within 3 months, he has issued a disclaimer that antibody titers cannot be used as sole diagnostic method.
• 1977: The relationship between FIP virus and other animal and human coronaviruses is documented.
• 1980: Immune enhancement by previous coronavirus exposure and with passive antibodies is reported. During this period, the co-existence of at least 2 distinct coronaviruses (feline enteric coronavirus and feline infectious peritonitis) is documented.
• 1981: Pedersen proposes that FIPV maybe a mutant form of FECV. It took many years to prove and became generally accepted by the time of the 1st International FECV/FIP Conference.
• 1983: Efforts to develop a live virus vaccine were unsuccessful.
• 1984: Feline coronavirus serotypes I and II were identified. Type I represents 80-95% of isolates and is specific to cats, while Type II represents 5-20% of isolates and arises through recombination with canine coronavirus.
• 1987: Raoul deGroot, University of Utrecht, sequences FIPV and for the first time we know its molecular structure.
• 1989: Cornell University researchers, including C.A. Stoddard and F.W. Scott, demonstrated that virulence of FIPV is proportional to its ability to replicate in macrophages.
• 1990: Temperature sensitive mutant intranasal vaccine was introduced.
• 1995: Subunit vaccines were evaluated but some caused an enhanced response in cats challenged with virulent virus..
• 1996-1998: Researchers at UC Davis and the University of Utrecht prove that FIPV arise as mutants of FECV.
• 1998: Janet Foley at UC Davis identified a genetic susceptibility to FIP.

A casual conversation at break including Raoul DeGroot (Utrecht), Al LeGendre (University of Tennessee) and Peter Rottier (Utrecht).

Even though we now have a much better understanding of FIPV and FIP, good diagnostics and effective therapies continue to elude us. At present, no serologic or PCR based diagnostic test will accurately and consistently diagnose the infection. Therefore, diagnosis continues to rely on clinical histories and a diversity of clinical abnormalities, including high coronavirus antibodies, typical fluid effusions in abdomen or chest, high gamma globulin, low lymphocyte levels, and high neutrophil numbers. Examination of biopsy specimens, especially when combined with immunohistochemical staining, remains the best method for definitive diagnosis of dry FIP. No treatment is known to appreciably alter the course of FIP, once it becomes clinically apparent.

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Presentation 1.2:
Living with Feline Coronavirus
Presenter: Sue Perry

Sue Perry is a cat owner from Great Britain whose cats have been living with feline enteric coronavirus for over seven years. Her veterinarian initially recommended that she euthanize all her cats since four tested positive for coronavirus. The veterinarian was convinced the remaining five would become positive and therefore they should also be euthanized. Fortunately, a young veterinarian recommended she contact Dr. Diane Addie. Since then, Sue has worked closely with Dr. Addie and she shared her experiences with the audience. As she said, when first learning that one of her cats might have FIP, she described it as a "shapeless horror." She has since learned to live with the coronavirus in her home and uses heightened levels of hygiene and divides her cats into different living groups depending on their coronavirus titers. Since the initial diagnosis in 1995, only one of her cats has died of FIP and only two still test positive for coronavirus. Her biggest advice to other cat owners is "DON'T PANIC."

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