# Transcriptomic analysis of Crandell-Rees feline kidney cell infections with field and vaccine feline calicivirus strains

## TL;DR

This study compares how different strains of feline calicivirus affect gene expression in kidney cells, revealing how virulence influences host responses.

## Contribution

The study reveals how virulent and vaccine strains of FCV differentially alter host gene expression, providing insights into calicivirus pathogenesis.

## Key findings

- Both field and vaccine FCV strains upregulated inflammatory genes like TNF-α and SELE.
- Field strain uniquely altered membrane signaling and cytoskeletal organization, while vaccine strain affected chromatin organization and mitochondrial metabolism.
- CRFK cells are effective in vitro models for studying FCV-induced host responses and pathogenesis.

## Abstract

•FCV infections in CRFK cells show the effects of strain virulence on host responses.•Field and vaccine strains upregulated inflammatory genes, such as TNF-α and SELE.•PI3K pathway inhibitors were downregulated during FCV infection.•Interleukin and histone genes were differentially expressed between FCV strains.•CRFK cells are relevant in vitro models to study FCV pathogenesis and host response.

FCV infections in CRFK cells show the effects of strain virulence on host responses.

Field and vaccine strains upregulated inflammatory genes, such as TNF-α and SELE.

PI3K pathway inhibitors were downregulated during FCV infection.

Interleukin and histone genes were differentially expressed between FCV strains.

CRFK cells are relevant in vitro models to study FCV pathogenesis and host response.

Feline upper respiratory tract disease (URTD) is a significant health concern in crowded environments, such as catteries and shelters. Feline calicivirus (FCV), which is endemic in domestic cats, is a major contributor to URTD and can cause a range of diseases that vary in severity. Unlike many other caliciviruses, including human caliciviruses and noroviruses, FCV replicates efficiently in cell culture and is a well-established model for studying calicivirus-host cell interactions. In this study, RNA-sequencing was used to characterise host and viral transcription profiles in Crandell-Rees feline kidney (CRFK) cells infected with either the attenuated F9 vaccine strain or a virulent field strain associated with virulent systemic FCV (VS-FCV) disease. At six hours post-infection, both strains induced the upregulation of inflammatory and stress response pathways, while genes involved in metabolism, cell signalling, and extracellular matrix maintenance were downregulated. Between field and vaccine strains, pathways related to membrane signalling and cytoskeletal organisation were uniquely altered in the field strain, while the F9 vaccine strain distinctly altered chromatin organisation, cytokine signalling and mitochondrial metabolism. These findings demonstrate the virulence of FCV strains differentially influences host gene expression in CRFK cells, which may inform host-pathogen interactions that contribute to FCV pathogenesis and variations in disease outcomes.