Foot-and-mouth disease virus infection inhibits LGP2 protein expression to exaggerate inflammatory response and promote viral replication

Cell Death Dis. 2017 Apr 13;8(4):e2747. doi: 10.1038/cddis.2017.170.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cricetinae
  • Foot-and-Mouth Disease Virus / physiology*
  • Foot-and-Mouth Disease* / enzymology
  • Foot-and-Mouth Disease* / immunology
  • Gene Expression Regulation, Enzymologic / immunology*
  • HEK293 Cells
  • Humans
  • Immunity, Innate / physiology*
  • RNA Helicases* / biosynthesis
  • RNA Helicases* / immunology
  • RNA, Viral / immunology
  • RNA, Viral / metabolism
  • Swine
  • Viral Proteins / immunology
  • Viral Proteins / metabolism
  • Virus Replication / physiology*

Substances

  • RNA, Viral
  • Viral Proteins
  • RNA Helicases