3 research outputs found
Host Gene Expression of Macrophages in Response to Feline Coronavirus Infection
Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate not only in enterocytes of the intestines but also in monocytes, subsequently systemically transporting the virus. The immune status and genetics of affected cats certainly play an important role in the pathogenesis. Considering the importance of genetics and host immune responses in viral infections, the goal of this study was to elucidate host gene expression in macrophages using RNA sequencing. Macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed a differential host gene expression. Despite the virus uptake, aligned viral reads did not increase from 2 to 17 h. The overlap of host gene expression among macrophages from different cats was limited, even though viral transcripts were detected in the cells. Interestingly, some of the downregulated genes in all macrophages were involved in immune signaling, while some upregulated genes common for all cats were found to be inhibiting immune activation. Our results highlight individual host responses playing an important role, consistent with the fact that few cats develop feline infectious peritonitis despite a common presence of enteric FCoV
CRFK and Primary Macrophages Transcriptomes in Response to Feline Coronavirus Infection Differ Significantly
Coronaviruses are highly infectious and common in many species, including in humans, and agricultural and domestic animals. Host responses play an important role in viral entry, replication, assembly, and pathogenesis, although much is still to be understood, particularly host–virus interactions. Feline coronavirus is highly contagious, and ubiquitous in virtually all cat populations. Host-pathogen interactions have not been studied extensively due to the complex pathogenesis and development of clinical disease. Few studies have investigated cellular host responses to feline coronavirus infection, particularly at early time points. Transcriptome studies based on next-generation sequencing have the potential to elucidate the early responses of cells after viral infection and, consequently, give further insight into the pathogenesis of viruses. The current study aims to characterize and compare the viral- and immune-related differentially expressed genes in response to the coronavirus FIPV across different time points in a cell line which is permissive for productive replication versus primary cells implicated in pathogenesis. When comparing host responses in Crandell-Rees Feline Kidney (CRFK) cells to primary macrophages, many differences were observed with regards to expressed genes and their enrichments for both KEGG pathways and GO terms. CRFK cells which are permissive for productive replication of feline infectious peritonitis virus, showed induction of a large network of immunological and virally induced pathways. In contrast, Macrophages did not show similar host responses, with stronger pathway enrichment in downregulated transcripts. This study provides insights to better understand gene transcription in immune cells compared to epithelial cells discerning pathways relevant to pathogenesis in the early stages of infection