Host responses to feline coronavirus are significantly different in primary macrophages compared to CRFK cells.

Abstract

Abstract Feline coronavirus (FCoV) is a highly contagious virus that exists as two pathotypes, with feline infectious peritonitis (FIP) caused by the pathogenic FIPV. The pathogenesis of FIPV remains poorly understood, and several different theories are still being discussed. A strong argument can be made for a role of the immune status and genetics of affected cats in pathogenesis. Most studies have focused on viral entry or differential replication instead of host responses. Considering the importance of genetics and host immune responses in viral infections, transcriptome studies to elucidate host pathogen interactions in primary macrophages and Crandell-Rees Feline Kidney cells (CRFK) were performed by next-generation sequencing of mRNA. CRFK and macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed differential gene expression in response. While CRFK gene expression was enriched for many classical virally induced genes and pathway networks, gene expression in macrophages was quite different. Interestingly, some of the commonly downregulated genes in macrophages involved innate anti-viral factors, while upregulated genes fell within unexpected pathways, such as autophagy, cellular senescence and other cellular processes not directly linked to infection. Our results highlight how individual host responses play a strong role when exposed to the virus, consistent with the fact that cats developing feline infectious peritonitis are very young or old, immune suppressed or of a particular genetic background. This study will give more insight into interactions of FCoV with feline macrophages and contrast it with the responses of a cell line that readily replicates the virus.