Feline infectious peritonitis–the ultimate hypersensitivity (Proceedings)

FIP – nothing's ever simple....It is a multifactoral disease involving virus factors, host factors, and environmental factors. The virus of FIP is feline coronavirus (FCoV) – interestingly, it is required but not sufficient for FIP. Coronaviruses have a large RNA genome. They are enveloped with helical capsid. The spike protein in the envelope is used for cellular attachment – determines in part cellular tropism. The virus is transmitted via the fecal oral route. It initially infects the intestines, where it infects mature epithelia of villus tips. It may cause mild to severe enteritis. In many infections, viremia and systemic spread may occur. The virus targets monocytes, and may be found in most parenchymal organs. The majority of infected cats remain healthy despite the systemic spread. Efficient replication of FCoV in monocytes and macrophages is a requirement for FIP development.

Coronaviruses mutate frequently – an infected cat may have a "cloud" of variants - viruses that differ genetically and/or antigenically have been identified within a single host. These changes may lead to change in virulence of the virus. However, no specific mutation has been identified that consistently correlates with disease production.

Host factors are important as well, specifically, the character and magnitude of the immune response to the virus. There appears to be a genetic predisposition, with heritability along familial lines. Concurrent disease can also predispose, especially immunosuppressive disease such as FeLV or FIV infection (affects CMI). FIP is often precipitated by 'stressful' episode (affects CMI).Cats that develop FIP have an exaggerated humoral response. The inflammation induced by virus and virus-infected cells produces the lesions of FIP.

Lymphocytes, specifically T lymphocytes undergo apoptosis in cats with FIP. This is not due to virus infection of these cells – so what's the mechanism? Cytokine production/imbalance? At least one study (Regan, A. D., et al., Virology, Nov 2008) has shown that virus infection leads to alteration of intra-cellular signaling pathways in infected monocytes. This in turn leads to production of pro-inflammatory cytokines.

Tests for FCoV cannot distinguish infection with avirulent vs. virulent FCoV thus no test specific for FIP exists. Serology is often used as a diagnostic aid, but caution is required in interpretation of FCoV serologic results - magnitude does NOT always correlate, i.e. a cat with FIP may have a low or even negative titer, and healthy cats exposed to or infected with FCoV may have very high titers. Serology assessing the response to a specific viral protein, the 7b protein was speculated to be specific for FIP. However, the presence of 7b-specific antibodies cannot confirm the FIP diagnosis, as cats with other conditions, as well as healthy cats, may be 7b seropositive. Virus-specific assays have also not shown specificity for the diagnosis of FIP. Is there a consistent difference between the "evil twin" and the "good twin" that can be exploited in a specific assay? There may be no single virus factor that consistently correlates with virulence that could be exploited in an FIP-specific assay; host factors are important. Diagnosis remains a combination of parameters.

Various therapies have been tried for FIP. Immunosuppressive drugs to reduce the inflammation and control the immune response may ameliorate some of the signs. Nonspecific immune Interferon has not shown success in treatment of FIP. A new treatment using a T lymphocyte stimulator has shown some promise.

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