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Feline infectious peritonitis (FIP) is a complex immune-mediated disease caused by feline coronavirus (FCoV). Despite advancements in understanding its pathogenesis, challenges persist in elucidating viral factors related to virion composition and replication. This study examined FCoV-infected cats with and without FIP for potential associations with or variation in expression ratios for different viral genes. We analyzed tissue samples with FIP lesions from 46 cats with FIP and mesenteric lymph nodes from 10 FCoV-infected cats (7b RT-qPCR positive) without FIP with three RT-qPCR assays, targeting (sub)-genomic RNAs of the RNA-dependent RNA polymerase (RdRp) and envelope (E) genes. In cats with FIP, the RdRp mRNA assay yielded the highest copy numbers, followed by the combined RdRp gRNA and mRNA assay; the E mRNA assay yielded the lowest copy numbers. In cats without FIP, significantly fewer viral RNA copies were detected regardless of the assay. Viral gene expression was not detected in six and was observed only at low levels in one or more assays in four samples. The observed correlation between assays and the intragroup correlation assay indicate consistent transcription of both the structural E protein and RdRp genes within FIP lesions in cats with FIP but not in cats with systemic FCoV infection alone. more...

Feline infectious peritonitis (FIP) is a fatal disease in cats caused by infection with feline coronavirus (FCoV). Despite severe inflammatory changes, defense mechanisms fail to achieve virus clearance. Some studies focused on various immune evasion mechanisms, but none of these studies elucidated the inefficacy of the complement system, which is one major player in FIP-associated immune pathogenesis. This study aimed to investigate the involvement of complement-regulating factors (CRFs). CRFs help modulate the immune response and prevent host tissue damage. Archived tissue samples from 31 deceased, FIP-affected cats were evaluated using multiplex immunohistochemistry for the spatial expression of the complement-regulating factors CD46 and CD59 in association with FIP lesions and their colocalization with complement-activating factor C1q and membrane attack complex C9 in relation to the presence and proximity of FCoV-infected cells. The FIP lesions of all 31 cats exhibited marked expression of both complement-regulating factors in proximity to FCoV-infected macrophages. Moreover, their expression in all 31 animals was significantly lower than the expression of the complement-activating factors C1q and C9 compared to areas farther distal to FCoV-infected cells. In conclusion, FCoV-infected macrophages in cats with FIP appear to use autocrine and paracrine expression of complement-regulating factors in their immediate environment to shield themselves from destruction by the complement system. more...

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective., Competing Interests: The authors declare that they have no conflict of interest. The GS-441524 tablets were provided by BOVA Specials, London, UK, but BOVA played no role in the interpretation of study data or the decision to submit the manuscript for publication. No commercial conflict of interest exists as the information is solely for scientific dissemination. more...

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL TM ) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was <5% and <15%, respectively; and AGP was stable in serum stored for at least 8 days at room temperature, at 4 °C and at -20 °C. Cats with confirmed FIP had significantly higher serum AGP concentrations (median: 2954 µg/mL (range: 200-5861 µg/mL)) than those with other inflammatory diseases (median: 1734 µg/mL (305-3449 µg/mL)) and clinically healthy cats (median 235 µg/mL (range: 78-616 µg/mL); p KW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP ( p MWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCL TM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment's effectiveness and identify potential relapses at an early stage. more...