Differential IFN-α/β production suppressing capacities of the leader proteins of mengovirus and foot-and-mouth disease virus

Abstract

Picornaviruses encompass a large family of RNA viruses. Some picornaviruses possess a leader (L) protein at the N-terminus of their polyprotein. The L proteins of encephalomyocarditis virus, a cardiovirus, and foot-and-mouth disease virus (FMDV), an aphthovirus, are both dispensable for replication and their major function seems to be the suppression of antiviral host cell responses. Previously, we showed that the L protein of mengovirus, a strain of encephalomyocarditis virus, inhibits antiviral responses by inhibiting type I interferon (IFN-α/β) gene transcription. The L protein of the FMDV is a protease (Lpro) that cleaves cellular factors to reduce cytokine and chemokine mRNA production and to inhibit cap-dependent cellular host mRNA translation, thereby limiting the production of proteins with antiviral activity. In this study, we constructed a viable chimeric mengovirus that expresses FMDV Lpro in place of the authentic L protein in order to compare the efficiency of the immune evasion mechanisms mediated by L and Lpro respectively. We show that in this mengovirus background the L protein is more potent than FMDV Lpro in suppressing IFN-α/β responses. Yet, FMDV Lpro is important to antagonize infection-limiting responses both in vitro and in vivo. © 2009 Blackwell Publishing Ltd.