Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements.

Yuan Gao,Hui-Chen Guo,Shi-Qi Sun

doi:10.1186/s12985-016-0561-z

Abstract

Foot-and-mouth disease virus (FMDV) represses host translation machinery, blocks protein secretion, and cleaves cellular proteins associated with signal transduction and the innate immune response to infection. Non-structural proteins (NSPs) and non-coding elements (NCEs) of FMDV play a critical role in these biological processes. The FMDV virion consists of capsid and nucleic acid. The virus genome is a positive single stranded RNA and encodes a single long open reading frame (ORF) flanked by a long structured 5ʹ-untranslated region (5ʹ-UTR) and a short 3ʹ-UTR. The ORF is translated into a polypeptide chain and processed into four structural proteins (VP1, VP2, VP3, and VP4), 10 NSPs (Lpro, 2A, 2B, 2C, 3A, 3B1–3, 3Cpro, and 3Dpol), and some cleavage intermediates. In the past decade, an increasing number of studies have begun to focus on the molecular pathogenesis of FMDV NSPs and NCEs. This review collected recent research progress on the biological functions of these NSPs and NCEs on the replication and host cellular regulation of FMDV to understand the molecular mechanism of host–FMDV interactions and provide perspectives for antiviral strategy and development of novel vaccines.

Highlights

Foot-and-mouth disease (FMD), an acute highly contagious viral disease in susceptible cloven-hoofed animals, was described 100 years ago
FMD virus (FMDV) Lpro generally functions as a multifunctional protein that blocks IFN-mediated antiviral response via multiple distinct mechanisms (Fig. 4): (1) Lpro shuts off host cell translation through cleavage of the translation initiation factor eIF4G, suppressing IFN protein expression [93]; (2) Lpro represses IFN activity by inhibiting activation of central upstream regulatory factors, including NFkB and IRF-3/7 [82]; and (3) Lpro acts as a DUB and cleaves ubiquitin chains from RIG-I, TBK1, TRAF3, and TRAF6, thereby inhibiting type I IFN signaling [85]
An antiviral compound and a molecular antagonist against protein 2C can inhibit viral RNA synthesis in picornavirus-infected cells, and virus strains containing guanidine-resistant 2C mutation cannot be inhibited by guanidine hydrochloride, providing direct evidence that FMDV 2C protein plays a key role in virus replication [123, 124]

Summary

Introduction

Foot-and-mouth disease (FMD), an acute highly contagious viral disease in susceptible cloven-hoofed animals, was described 100 years ago. Translation of FMDV RNA The featured IRES element is an essential structural region for initiation of protein synthesis in picornavirus genome RNA [25, 35, 36].

Results

Conclusion