Host RNA dynamics in cats with feline infectious peritonitis

Feline infectious peritonitis (FIP) is a fatal disease, if left untreated, caused by feline coronavirus (FCoV). Although the role of the immune system in the pathogenesis of FIP remains incompletely understood, an excessive and harmful immune response appears to be a key factor. In a recent study by the same authors, 18 cats with FIP were successfully cured with oral GS-441524. The present study aimed to analyze the molecular signatures of these treated cats using next-generation RNA-sequencing on full blood samples by highlighting key immune pathways involved in disease progression, treatment response, and recovery. Therefore, samples were analyzed at three stages: untreated (d0), treated with the antiviral drug (days 2, 7, 28), and fully cured (days 168, 252, 365). Additionally, gene expression profiles were compared to those of healthy FCoV-infected control cats (n=12) and uninfected healthy control cats (n=5). Multiple tests with adjusted p-value (adj.p<0.001) were performed. Within the first few days of treatment, massive changes in the RNA signature profile were observed, with approximately 75% of expressed genes significantly differentially regulated between d0 and later time points. Notably, a strong antiviral immune response, which was dominant at the onset of the disease, was significantly downregulated within two days, accompanied by a shift in blood cell composition from monocytes and neutrophils to B cells. Our findings revealed a rapid normalization of the blood RNA signature within the first week of treatment suggesting that elimination of the virus from the blood leads to a rapid down-regulation of the damaging immune response. RNA sequencing of feline whole blood in cats with feline infectious peritonitis before, during and after antiviral treatment