Identification of Feline Interferon Regulatory Factor 1 as an Efficient Antiviral Factor against the Replication of Feline Calicivirus and Other Feline Viruses.

Yongxiang Liu,Jin Tian,Hongtao Kang,Xiaoxiao Liu,Xiaoliang Hu,Jiasen Liu,Liandong Qu

doi:10.1155/2018/2739830

Abstract

Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed. Further, we found that IRF1 was localized in the nucleus and efficiently activated IFN-β and the ISRE promoter. IRF1 can trigger the production of endogenous interferon and the expression of ISGs, suggesting that IRF1 can positively regulate IFN signalling. Importantly, the mRNA and protein levels of IRF1 were reduced upon FCV infection, which may be a new strategy for FCV to evade the innate immune system. Finally, the antiviral activity of IRF1 against feline panleukopenia virus, feline herpesvirus, and feline infectious peritonitis virus was demonstrated. These data indicate that feline IRF1 plays an important role in regulating the host type I IFN response and inhibiting feline viral infections.

Highlights

Feline calicivirus (FCV) is a highly contagious pathogen of cats and usually causes mild to serious oral and upper respiratory tract disease [1]
To explore which feline IFN-stimulated genes (ISGs) could inhibit the replication of FCV, ten feline ISGs with antiviral activities that have been described were cloned into the p3×FlagCMV10 vector
These data showed that feline interferon regulatory factor 1 (IRF1) is a potent inhibitor for FCV

Summary

Introduction

Feline calicivirus (FCV) is a highly contagious pathogen of cats and usually causes mild to serious oral and upper respiratory tract disease [1]. Recent studies indicated that limited HuNoV replication can occur in immortalised B cells [4, 5], this may not be a perfect cellular model for research about the characteristics of HuNoV. The nonstructural protein p39 of the FCV F4 strain could suppress the production of IFN-β by preventing IRF3 activation [8]. Our earlier study found that infection of FCV-2280 led to a robust release of IFN-β, but other FCV strains failed [7]. The FCV strain 2280 proteinase-polymerase (PP) protein suppresses luciferase reporter gene expression driven by endogenous and exogenous promoters, which contributes to the inhibition of host cell transcription [6]

Methods

Results

Conclusion