Comparative transcriptome analysis of PBMCs in cats diagnosed with and recovered from FIPV

对确诊和康复的猫传染性单核细胞增多症(FIPV)患者外周血单核细胞(PBMC)进行比较转录组分析。

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Abstract

BACKGROUND: Feline infectious peritonitis is a viral disease caused by feline coronavirus an enveloped virus with a single-stranded RNA genome that is approximately 30 kb long. Although FCoV generally causes mild symptoms, approximately 5% of cases progress to death in cats worldwide. FCoV shares certain virological features with severe acute respiratory syndrome coronavirus 2 that causes COVID-19, indicating that common therapeutic strategies may be applicable. GS-441524 the parent drug of remdesivir and a competitive inhibitor of nucleoside triphosphates in viral RNA synthesis is a well-known treatment for FIP. However, comparative transcriptome and gene ontology analyses of normal (Normal), FIP-diseased (FIPD), and FIP-recovered (FIPR) cats have not yet been conducted. RESULTS: In this study, we compared the mRNA expression profiles of peripheral blood mononuclear cells from Normal, FIPD, and FIPR cats to identify immunological alterations. We identified 677 (FIPD/Normal) and 431 (FIPR/FIPD) differentially expressed genes with statistical significance. These data were input into the bioinformatics program. As a result, the analysis revealed statistically significant and contrasting patterns of canonical pathways of neutrophil degranulation and interleukin-8 (IL-8) signaling pathways. Additionally, we observed that kruppel-like factor 6 (KLF6) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were upstream molecules of IL-8, promoting neutrophil activation and function. CONCLUSIONS: This study identified immunological alterations in PBMCs of Normal, FIPD, and FIPR cats. KLF-6 and NF-κB were found to regulate IL-8-mediated neutrophil activation.

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