» Articles » PMID: 28662438

Foot-and-mouth Disease Virus Induces Lysosomal Degradation of Host Protein Kinase PKR by 3C Proteinase to Facilitate Virus Replication

Overview
Journal Virology
Specialty Microbiology
Date 2017 Jun 30
PMID 28662438
Citations 33
Authors
Affiliations
Soon will be listed here.
Abstract

The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3C proteinase (3C) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C or 3C-induced shutoff of host protein synthesis. We show that 3C induces PKR degradation by lysosomal pathway and no interaction is determined between 3C and PKR. Together, our results indicate that PKR acts an important antiviral factor during FMDV infection, and FMDV has evolved a strategy to overcome PKR-mediated antiviral role by downregulation of PKR protein.

Citing Articles

The Strategies Used by Animal Viruses to Antagonize Host Antiviral Innate Immunity: New Clues for Developing Live Attenuated Vaccines (LAVs).

Chen N, Zhang B Vaccines (Basel). 2025; 13(1).

PMID: 39852825 PMC: 11768843. DOI: 10.3390/vaccines13010046.


Knockout of the WD40 domain of ATG16L1 enhances foot and mouth disease virus replication.

Wu X, Yang Y, Ru Y, Hao R, Zhao D, Ren R BMC Genomics. 2024; 25(1):796.

PMID: 39179961 PMC: 11342673. DOI: 10.1186/s12864-024-10703-6.


Preventive effects of quercetin against foot-and-mouth disease virus and by inducing type I interferon.

Lee G, Kang H, Kim A, Park J, Lee M, Kim S Front Microbiol. 2023; 14:1121830.

PMID: 37250022 PMC: 10213290. DOI: 10.3389/fmicb.2023.1121830.


African swine fever virus pS273R antagonizes stress granule formation by cleaving the nucleating protein G3BP1 to facilitate viral replication.

Li T, Li X, Wang X, Chen X, Zhao G, Liu C J Biol Chem. 2023; 299(7):104844.

PMID: 37209818 PMC: 10404608. DOI: 10.1016/j.jbc.2023.104844.


Host-Specific Interplay between Foot-and-Mouth Disease Virus 3D Polymerase and the Type-I Interferon Pathway.

Sarry M, Caignard G, Dupre J, Zientara S, Vitour D, Bakkali Kassimi L Viruses. 2023; 15(3).

PMID: 36992375 PMC: 10054395. DOI: 10.3390/v15030666.


References
1.
Liu Y, Zhu Z, Zhang M, Zheng H . Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses. Vet Res. 2015; 46:127. PMC: 4625562. DOI: 10.1186/s13567-015-0273-1. View

2.
Steinberger J, Skern T . The leader proteinase of foot-and-mouth disease virus: structure-function relationships in a proteolytic virulence factor. Biol Chem. 2014; 395(10):1179-85. PMC: 4931897. DOI: 10.1515/hsz-2014-0156. View

3.
Lu Y, Wambach M, Katze M, KRUG R . Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology. 1995; 214(1):222-8. DOI: 10.1006/viro.1995.9937. View

4.
Wang S, Chi X, Wei H, Chen Y, Chen Z, Huang S . Influenza A virus-induced degradation of eukaryotic translation initiation factor 4B contributes to viral replication by suppressing IFITM3 protein expression. J Virol. 2014; 88(15):8375-85. PMC: 4135930. DOI: 10.1128/JVI.00126-14. View

5.
Tan S, Gale Jr M, Katze M . Double-stranded RNA-independent dimerization of interferon-induced protein kinase PKR and inhibition of dimerization by the cellular P58IPK inhibitor. Mol Cell Biol. 1998; 18(5):2431-43. PMC: 110623. DOI: 10.1128/MCB.18.5.2431. View