Host Transcriptome Studies in Response to Feline Coronavirus Reveal Differences in Macrophages vs CRFK

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 strains remains an enigma, and several different theories are still being discussed. A predominant theory has been that the pathogenic FIPV arises from a mutation of the enteric form, so that it could replicate not only in enterocytes of the intestines but also in monocytes, which subsequently transported the virus systemically. A strong argument can also be made for a role of the immune status and genetics of affected cats in pathogenesis. While some studies have looked at ex vivo infection of macrophages with virulent and avirulent strains, most of these studies focus 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 macrophages and CRFK at different time points 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 pathways, gene expression in macrophages was quite different. Instead, macrophage responses were very individual and showed limited overlap among cats. 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.