Abstract
The role of the innate immune protein LGP2 (laboratory of genetics and physiology 2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression but reduced protein expression. Overexpression of LGP2 suppressed FMDV replication, and the inflammatory response was significantly inhibited by LGP2 in virus-infected cells. The N-terminal DExDc and the C-terminal regulatory domain regions of LGP2 were essential for LGP2-mediated antiviral activity against FMDV. Disruption of RNA recognition by LGP2 is suggested to abolish completely LGP2-mediated antiviral activity against FMDV. FMDV leader protein (Lpro), as well as the 3Cpro and 2B proteins were determined to possess the ability to induce reduction of LGP2 protein expression. 2B-induced reduction of LGP2 was independent of cleavage of eukaryotic translation initiation factor 4 gamma; and the proteasomes, lysosomes or caspase-dependent pathways were not involved in this process. The C-terminal amino acids of 101–154 were essential for 2B-induced reduction of LGP2 and upregulation of inflammatory response. Direct interaction was demonstrated between LGP2 and 2B. Our results describe the antiviral role of LGP2 against FMDV and a novel antagonistic mechanism of FMDV that is mediated by 2B protein.
Highlights
Foot-and-mouth disease is an acute and highly contagious disease of cloven-hooved animals, and affects pigs and cattle
To explore the potential role of LGP2 during Foot-and-mouth disease virus (FMDV) infection, we first investigated the state of LGP2 in FMDV-infected cells
PK-15 cells were infected by FMDV at an multiplicity of infection (MOI) of 0.5, and the dynamics of LGP2 were determined
Summary
Foot-and-mouth disease is an acute and highly contagious disease of cloven-hooved animals, and affects pigs and cattle. The activated innate immune system results in the expression of various antiviral proteins and subsequently induces a series of antiviral responses to suppress viral replication.[11]. Toll-like receptors, retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), NOD-like receptors and C-type lectin receptors. These pattern-recognition receptors trigger intracellular signalling cascades by different pathways.[12] RLRs are a family of DExD/H box RNA helicases containing RIG-I, melanoma differentiation-associated protein (MDA)-5 and LGP2 (laboratory of genetics and physiology 2); all of which include a DExD/H box helicase domain.[14] the three RLRs can show different roles during various viral infections.[15]. LGP2 is a homologue of RIG-I and MDA5, but lacks the caspase activation and recruitment domain and is currently thought to function differentially with RIG-I- and MDA5mediated functions.[16,17]
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