The Effect of Natural Feline Coronavirus Infection on the Host Immune Response: A Whole-Transcriptome Analysis of the Mesenteric Lymph Nodes in Cats with and without Feline Infectious Peritonitis.

Alexandra J Malbon,Anja Kipar,Carole Burgener,Giancarlo Russo,Marina L Meli,Emi N Barker,Séverine Tasker

doi:10.3390/pathogens9070524

Alexandra J Malbon, Anja Kipar + Show 5 more

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https://doi.org/10.3390/pathogens9070524

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Journal: Pathogens	Publication Date: Jun 29, 2020
Citations: 6	License type: CC BY 4.0

Affiliation: University of Zurich, University of Bristol

Abstract

Feline infectious peritonitis (FIP) is a coronavirus-induced disease of cats, in which the immune system is known to play a crucial, but complex, role in the pathogenesis. This role is still incompletely understood, with involvement of both host and viral factors. To evaluate differential gene expression and pathway involvement in feline coronavirus (FCoV) infection and FIP, we applied next-generation RNA-sequencing of the mesenteric lymph nodes from cats with naturally-acquired FIP, as well as those with systemic FCoV infection without FIP, and those with neither. Viral infection was associated with upregulation of viral defenses regardless of the disease state, but to a greater degree in FIP. FIP was associated with higher pro-inflammatory pathway enrichment, whilst non-FIP FCoV-positive cats showed lower enrichment of humoral immunity pathways, below that of uninfected cats in the case of immunoglobulin production pathways. This host response is presumed to be protective. In FIP, downregulation of T cell-related processes was observed, which did not occur in non-FIP FCoV-positive cats. These results emphasize the importance of the host’s immune balance in determining the outcome of the FCoV infection.

Highlights

Feline infectious peritonitis (FIP) is a fatal immune-mediated disease of domestic and wild felids caused by feline coronavirus (FCoV), a highly prevalent virus with a worldwide distribution which infects domestic and wild felids
A Venn diagram (Figure 7) shows that of all significant Differentially expressed (DE) genes in the two comparisons, 2094 are significant only in the FIP comparison (G2 vs. G1_Neg), 51 only in the comparison between FCoV-positive and FCoV-negative subgroups of non-FIP cats (G1_Pos vs. G1_Neg), and 66 overlapped. Each of these sets of genes was further split by direction of their dysregulation
The results of the present study for the first time provide detailed information on how the immune system responds to FCoV infection in natural cases, both in animals succumbing to FIP and those showing no clinical or pathological signs attributable to FIP

Summary

Introduction

Feline infectious peritonitis (FIP) is a fatal immune-mediated disease of domestic and wild felids caused by feline coronavirus (FCoV), a highly prevalent virus with a worldwide distribution which infects domestic and wild felids. FCoV is an alphacoronavirus, similar to several respiratory and enteric. CoV, and the ‘common cold’ CoVs of humans It differs at the genus level from the betacoronaviruses that include the severe respiratory disease-causing CoVs of humans (SARS-CoV 1 and 2, MERS-CoV), and the gammacoronaviruses of birds. FCoV initially infects enterocytes via the fecal-oral route and in most cases causes only a mild or subclinical enteric disease. In ~5% of infected cats, a combination of, as yet only partially understood viral and host factors lead to the development of FIP [5,6]. FIP is characterized by (pyo) granulomatous phlebitis, generally accompanied by more extensive pyogranulomatous lesions and, in many cases, cavitary effusions [7,8,9]

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