From the FCoV carrier state to FIP
What leads from infection to disease, from the chronic FCoV carrier state to FIP? This question will be asked by anybody who hears the classical anamnesis of a kitten obtained from a bona-fide breeder, kept in isolation from other cats that succumbed to FIP some weeks after the purchase.

The key pathogenic event in FIP is the infection of monocytes and macrophages. We formerly thought that avirulent FCoV strains remain confined to the digestive tract and would not spread beyond the intestinal epithelium and regional lymph nodes while virulent strains would disseminate to other organs via blood-borne monocytes. This idea can no longer be sustained, in view of the PCR results in healthy cats quoted above - the difference must rather be a quantitative one. In vitro, the virulence of FCoV strains was indeed correlated with their ability to infect cultured peritoneal macrophages. When strains were compared, however, the avirulent ones infected fewer macrophages and produced lower virus titres than virulent strains. Moreover, the avirulent strains were less able to sustain viral replication and to spread to other macrophages. This is no black-and-white phenomenon, rather a gradual transition, as the course of FIP is not uniform.

There is ample evidence for an involvement of the immune system in the pathogenesis of FIP. Humoral immunity is obviously not protective. FCoV-seropositive cats that are experimentally infected with FIPV often develop an accelerated, fulminating course of the disease, leading to the 'early death' phenomenon mentioned above. Clinical signs and lesions develop earlier, and the mean survival time is dramatically reduced as compared to seronegative cats. Direct evidence for the involvement of antibodies was obtained by transfusion of purified IgG from cat FCoV-antisera into cats, which indeed developed accelerated FIP upon experimental challenge. We also know, which antibodies are the killers: when vaccinia virus recombinants expressing singe gene products were used to immunize cats, 'early death' occurred only in the group that had seen the spike (S) protein before.

Most authors consider the vascular and perivascular lesions in FIP to be immune-mediated, but there is uncertainty about the actual pathogenetic mechanism. At least some vascular injury may be attributed to immune-mediated lysis of infected cells: FIPV-infected white blood cells were detected in the lumen, intima and wall of veins and in perivascular locations. Furthermore, inflammatory mediators such as cytokines, leukotrienes and prostaglandins that are released by infected macrophages could play a role in the development of the perivascular pyogranulomata. These products could induce vascular permeability changes and provide additional chemotactic stimuli for neutrophils and monocytes. In response to the inflammation, the attracted cells may release additional mediators and cytotoxic substances; the monocytes would also serve as new targets for FIPV. The end result would be enhanced local virus production and increased tissue damage.

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