Clinical data from 488 cats (1979-2000) with histopathologically confirmed feline infectious peritonitis (FIP) and 620 comparable controls were evaluated retrospectively to assess the value of several diagnostic tests frequently used in the evaluation of cats with suspected FIP. Diagnostic utility of serum albumin to globulin ratio for the diagnosis of FIP was greater than of the utility of serum total protein and gamma-globulin concentrations. Diagnostic utility of these variables was higher when performed on effusion. On effusion, positive and negative predictive values of Rivalta's test, a test that distinguishes between exudates and transudates (0.86 and 0.97), anti-coronavirus antibody detection (0.90 and 0.79), and immunofluorescence staining of coronavirus antigen in macrophages (1.00 and 0.57) were investigated. The positive and negative predictive values of presence of anti-coronavirus antibodies were 0.44 and 0.90, respectively, antibody concentrations (1:1,600) were 0.94 and 0.88. presence of immune complexes measured by a competitive enzyme-linked immunosorbent assay were 0.67 and 0.84, and detection of viral RNA by serum reverse-transcriptase polymerase chain reaction (RT-PCR) were 0.90 and 0.47. Effusion RT-PCR was performed in 6 cats; it was positive in all 5 cats with FIP and negative in the cat with another disease. Diagnostic assays on the fluid in cats with body effusion had good predictive values. Definitive diagnosis of FIP on the basis of measurement of various variables in serum was not possible. Serum tests can only be used to facilitate the decision for more invasive diagnostic methods.

Abstract. Feline infectious peritonitis (FIP) is a fatal, coronavirus (CoV)-induced systemic disease in cats, characterized by granulomas in organs and granulomatous vasculitis. This study describes the morphologic features of granulomatous vasculitis in FIP as well as its development in the course of monocyte-associated feline CoV (FCoV) viremia in five naturally infected Domestic Shorthair cats with FIP. Monocyte-associated FCoV viremia was demonstrated by immunohistology, RNA in situ hybridization, and electron micropscopy. Granulomatous phlebitis at different stages of development was observed. Vasculitic processes ranged from attachment and emigration of FCoV-infected monocytes to vascular/perivascular granulomatous infiltrates with destruction of the vascular basal lamina. Monocytes as well as perivascular macrophages were activated because they were strongly positive for CD18 and expressed cytokines (tumor necrosis factor-␣ and interleukin-1␤) and matrix metalloproteinase-9. In addition, general activation of endothelial cells, represented by major histocompatibility complex II upregulation, was observed in all cases. These results confirm FIP as a monocyte-triggered systemic disease and demonstrate the central role of activated monocytes in FIP vasculitis.Key words: Cats; feline coronavirus; feline infectious peritonitis; granulomatous vasculitis; monocyte-associated viremia; phlebitis.Feline infectious peritonitis (FIP) is a well-known and widely distributed coronavirus (CoV)-induced systemic disease in cats, characterized by fibrinous to granulomatous serositis with protein-rich effusions in body cavities and granulomatous inflammatory lesions in several organs. 24,45 Not the most obvious finding, but one of its morphologic hallmarks is a granulomatous to necrotizing phlebitis and periphlebitis. 8,16,24,43 Up till now, the pathogenesis of FIP is largely undetermined.Feline CoV (FCoV) is transmitted via the fecal-oral route and primarily infects enterocytes. 28 Despite the generally high prevalence of FCoV infection among the cat population, especially in multicat facilities, FIP morbidity is low and rarely surpasses 5%. 1,7,28 FIP seems to develop in the individual infected animal when FCoV acquires virulence by deletions in open reading frames 3 and 7, coding for nonstructural proteins of unknown function, which occur as mutations primarily during replication in the infected host. 39 Most infected cats develop an FCoV viremia that can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) on isolated (and cultivated) monocytes regardless of the development of FIP. 7,15 FCoV-1 Present address: Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool, UK infected circulating monocytes are considered as responsible for viral dissemination within the host. 10,11,28,44 Furthermore, the demonstration of FCoV antigen within intravascular leukocytes and among cells in the lesions of vasculitis in a previous experimental study suggested that the inf...

Twenty-three cats with spontaneous feline infectious peritonitis (FIP) were examined by light microscopy including immunohistology and histochemistry in order to determine the cellular composition and the expression of viral antigen in lesions in FIP. Furthermore, the presence of plasma-cells producing coronavirus-specific antibodies was evaluated in situ. Macrophages and neutrophils were demonstrated by an antibody against calprotectin (leukocyte protein L1, myeloid/histiocyte antigen), neutrophils were recognized due to their chloroacetate esterase activity, and B- and T-lymphocytes were identified by antibodies against the CD3 antigen and the CD45R antigen, respectively. Expression of viral antigen was immunohistologically demonstrated by a monoclonal antibody (mAb) against coronavirus while coronavirus-specific antibodies in situ were identified by the application of feline coronavirus prior to the coronavirus antibody. Lesions were classified as diffuse alterations at serosal surfaces, granulomas with areas of necrosis, granulomas without extended necrosis, focal and perivascular lymphoplasmocytic infiltrates, and granulomatous-necrotizing vasculitis. Diffuse alterations on serosal surfaces were represented either by activated mesothelial cells with single coronavirus antigen-bearing macrophages or by layers of precipitated exudate containing single to numerous granulomas with areas of necrosis. In liver and spleen, the exudate was often underlaid by a small band of subcapsular B-cells with an occasional plasma-cell producing coronavirus-specific antibodies. In other locations, a variably broad band of B-cells and plasma-cells, often infiltrating between underlying muscle fibers, separated the exudate from the unaltered tissue. Some of these plasma-cells were positive for coronavirus-specific antibodies. In granulomas with areas of necrosis, the central necrosis was surrounded by macrophages usually expressing considerable amounts of viral antigen. Few B-cells and plasma-cells were found in the periphery. In granulomas without extended necrosis, the number of macrophages were lower. Only few macrophages expressing low amounts of viral antigen were present. B-cells and plasma-cells formed a broad rim. Few plasma-cells stained positive for coronavirus-specific antibodies. In both types of granulomas, few neutrophils were found between macrophages. Few T-cells were seen scattered throughout the lesions. Focal and perivascular lymphoplasmocytic infiltrates were mainlyseen in omentum and leptomeninx. B-cells were the predominant cells; some plasma-cells were positive for coronavirus-specific antibodies. Viral antigen was not readily detected in these alterations. Granulomatous-necrotizing vasculitis was occasionally found in kidneys and leptomeninx. It was dominated by macrophages which often stained strongly positive for coronavirus antigen. Different types of alteration were often seen in the same animal and even the same tissue. There was no obvious correlation between the cat's age, gross pathological changes...

Specified pathogen-free cats were naturally infected with FCoV or experimentally infected with FCoV type I. Seroconversion was determined and the course of infection was monitored by measuring the FCoV loads in faeces, whole blood, plasma and/or monocytes. Tissue samples collected at necropsy were examined for viral load and histopathological changes. Experimentally infected animals started shedding virus as soon as 2 days after infection. They generally displayed the highest viral loads in colon, ileum and mesenteric lymph nodes. Seroconversion occurred 3-4 weeks post infection. Naturally infected cats were positive for FCoV antibodies and monocyte-associated FCoV viraemia prior to death. At necropsy, most animals tested positive for viral shedding and FCoV RNA was found in spleen, mesenteric lymph nodes and bone marrow. Both experimentally and naturally infected cats remained clinically healthy. Pathological findings were restricted to generalized lymphatic hyperplasia. These findings demonstrate the presence of systemic FCoV infection with high viral loads in the absence of clinical and pathological signs.

Different proteases from various microorganisms present in the respiratory tract were capable of enhancing influenza virus infectivity and pathogenicity in mice by proteolytic activation of hemagglutinin (HA). Aerococcus viridans, isolated from a patient with pneumonia, secreted a protease that could activate HA directly, similarly to some Staphylococcus aureus strains. The protease of Pseudomonas aeruginosa could not activate HA directly, but combined application of P. aeruginosa protease and virus into mice enhanced virus titers and pathogenicity. Generation of trypsin-like activity in bronchoalveolar lavage fluids resulting from this combination treatment may be responsible for HA activation. A similar indirect effect on HA activation was induced by streptokinase and staphylokinase, which are known to generate plasmin by plasminogen activation. It was concluded that plasminogen-activating streptococci and staphylococci facilitate viral replication and pathogenicity of plasmin-sensitive influenza virus strains by amplification of the plasminogen/plasmin system.