Advances in Foot-and-Mouth Disease Virus Proteins Regulating Host Innate Immunity.

Jiangling Peng,Dan Li,Jiamin Yi,Haixue Zheng,Wenping Yang,Jingjing Ren,Yuan Wen

doi:10.3389/fmicb.2020.02046

Abstract

Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoofed animals such as pigs, cattle, and sheep. The disease is caused by the foot-and-mouth disease virus (FMDV) which has a non-enveloped virion with icosahedral symmetry that encapsulates a positive-sense, single-stranded RNA genome of ∼8.4 kb. FMDV infection causes obvious immunosuppressive effects on the host. In recent years, studies on the immunosuppressive mechanism of FMDV have become a popular topic. In addition, studies have shown that many FMDV proteins are involved in the regulation of host innate immunity and have revealed mechanisms by which FMDV proteins mediate host innate immunity. In this review, advances in studies on the mechanisms of interaction between FMDV proteins and host innate immunity are summarized to provide a comprehensive understanding of FMDV pathogenesis and the theoretical basis for FMD prevention and control.

Highlights

Foot-and-mouth disease (FMD) is an acute, highly contagious livestock disease that affects clovenhoofed animals such as pigs, cattle, and sheep, thereby causing severe economic loss
Its genome, comprising of approximately 8,400 nucleotides, has a single open reading frame (ORF) that is translated into a polyprotein, which is processed by the three viral proteases Lpro, 2A, and 3Cpro into the polypeptide products P1 (VP1 to VP4), P2 (2A, 2B, and 2C), and P3 (3A, 3B, 3Cpro, and 3Dpol) and subsequently generated
Subsequent study found that VP3 plays a vital role in escaping the host’s innate immune response, for example, Foot-and-mouth disease virus (FMDV) VP3 can interact with janus kinase 1 (JAK1) and degrade it via the lysosomal pathway, thereby inhibiting IFN-γ-induced phosphorylation, signal transducer activator of transcription 1 (STAT1) dimerization and nuclear accumulation of phosphorylated STAT1, which leads to the inhibition of the type II IFN signaling pathway to evade the host innate immunity (Li et al, 2016b)

Summary

INTRODUCTION

Foot-and-mouth disease (FMD) is an acute, highly contagious livestock disease that affects clovenhoofed animals such as pigs, cattle, and sheep, thereby causing severe economic loss. Interferon (IFN) production plays a pivotal role in the host antiviral innate immune response, which can suppress viral replication especially in the early stage of the immune response. The FMDV RNA is recognized by MDA5 and induces type I IFN production in the host to inhibit FMDV replication (Stetson and Medzhitov, 2006; Ma et al, 2018). Innate immune cells play important roles in innate immune response processes, which can induce the production of IFNs in many ways to achieve antiviral effects (Golde et al, 2008). FMDV proteins can directly or indirectly regulate the host’s innate immune response to survive and replicate in the host (Rodriguez Pulido and Saiz, 2017). This article reviews the relationship between FMDV proteins and the host’s innate immune-related proteins and provides ideas for further studies regarding FMDV inhibiting the host’s innate immune response and regarding effective FMDV vaccines development

FMDV PROTEINS REGULATE HOST INNATE IMMUNITY

Advances in the Suppression of Innate Immunity by FMDV Lpro

Structural proteins