ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response

Abstract

The type I IFN-mediated immune response is the first line of antiviral defence. Coronaviruses, like many other viruses, have evolved mechanisms to evade this innate response, ensuring their survival. Several coronavirus accessory genes play a central role in these pathways, but for feline coronaviruses this has never to our knowledge been studied. As it has been demonstrated previously that ORF7 is essential for efficient replication in vitro and virulence in vivo of feline infectious peritonitis virus (FIPV), the role of this ORF in the evasion of the IFN-a antiviral response was investigated. Deletion of ORF7 from FIPV strain 79-1146 (FIPV-D7) rendered the virus more susceptible to IFN-a treatment. Given that ORF7 encodes two proteins, 7a and 7b, it was further explored which of these proteins is active in this mechanism. Providing 7a protein in trans rescued the mutant FIPV-D7 from IFN sensitivity, which was not achieved by addition of 7b protein. Nevertheless, addition of protein 7a to FIPV-D3D7, a FIPV mutant deleted in both ORF3 and ORF7, could no longer increase the replication capacity of this mutant in the presence of IFN. These results indicate that FIPV 7a protein is a type I IFN antagonist and protects the virus from the antiviral state induced by IFN, but it needs the presence of ORF3-encoded proteins to exert its antagonistic function.

Accessory proteins of SARS-CoV and other coronaviruses

“…The ORF3 proteins were found to have only supportive roles during infection of the target cell by FIPV (Dedeurwaerder et al, 2013). It has also been shown that the FIPV p7a protein is a type-I IFN antagonist but needs the presence of ORF3 proteins to fully exert its antagonistic function (Dedeurwaerder et al, 2014).…”

“…Extensive functional studies in cell culture and animal models have shown that SARS-CoV accessory proteins are involved in a wide variety of cellular processes, such as cell proliferation, programmed cell death, activation of stress response pathways and cytokine production, to name just a few. Notably, some coronaviral accessory proteins have also been shown to modulate the interferon signaling, which is of paramount importance for host antiviral immunity Dedeurwaerder et al, 2014;Zhang et al, 2013;Cruz et al, 2013).…”

Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats

“…Yet, recent studies proved that accessory proteins might have a wide range of functions including modulation of viral pathogenicity like ORF7 of TGEV, which absence increases cell RNA degradation and viral pathogenicity in infected piglets (Cruz et al, 2011). Others act as counteragents of the innate immunity like ORF7a of FCoV or ORF6 of SARS-CoV to name a few (Dedeurwaerder et al, 2014;Frieman et al, 2007). Some others are crucial in viral tropism.…”

Characterization of monoclonal antibodies against feline coronavirus accessory protein 7b

“…The functions of the FCoV-accessory proteins 3a-3c remain to be determined. Recently, it was suggested that the accessory protein 7a represents an interferon antagonist (Dedeurwaerder et al, 2014), although its expression in infected cells has not been confirmed. Among the FCoV-accessory proteins, the 7b protein has been studied most extensively.…”