The VP3 structural protein of foot‐and‐mouth disease virus inhibits the IFN‐β signaling pathway

Li, Dan; Yang, Wei; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Lian, Kaiqi; Lei, Cao-Qi; Li, Shu; Liu, Xiangtao; Zheng, Haixue; Shu, Hong‐Bing

doi:10.1096/fj.15-281410

Cited by 71 publications

(74 citation statements)

References 45 publications

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“…Previous studies have reported that picornaviruses exert various strategies to evade host innate immune responses through certain viral proteins, such as L pro , VP2, VP3, 2A pro , 2C pro , 3A pro , and 3C pro (17,18,(25)(26)(27)(28)(29)(30)(31). In this study, we found that the overexpression of SVV proteins VP2, 3C pro , and 3D reduced Sev-induced IFN-␤ production (Fig.…”

Section: Resultssupporting

confidence: 58%

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage

Qian

Fan

Liu

et al. 2017

J Virol

107

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Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-␤ (TRIF), and TRAF family member-associated NF-B activator (TANK), via viral 3C protease (3C pro ). SVV 3C pro mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-B activation. SVV was also found to be sensitive to IFN-␤. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules. IMPORTANCE Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the Picornavirus genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3C pro to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial for the Toll-like receptor 3 (TLR3)-mediated and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated signaling pathway. We also found that SVV is sensitive to IFN-␤. These findings increase our understanding of the interaction between SVV and host innate immunity.

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Section: Resultssupporting

confidence: 58%

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage

Qian

Fan

Liu

et al. 2017

J Virol

107

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“…The collected cells were then lysed and immunoprecipitated as described previously (27). For Western blotting, target proteins were resolved by SDS-PAGE and transferred onto an Immobilon-P membrane (Millipore).…”

Section: Methodsmentioning

confidence: 99%

Foot-and-Mouth Disease Virus Viroporin 2B Antagonizes RIG-I-Mediated Antiviral Effects by Inhibition of Its Protein Expression

Zhu

Wang

Yang

et al. 2016

J Virol

Self Cite

125

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The role of retinoic acid-inducible gene I (RIG-I) in foot-and-mouth disease virus (FMDV)-infected cells remains unknown. Here, we showed that RIG-I inhibits FMDV replication in host cells. FMDV infection increased the transcription of RIG-I, while it decreased RIG-I protein expression. A detailed analysis revealed that FMDV leader proteinase (Lpro), as well as 3C proteinase (3Cpro) and 2B protein, decreased RIG-I protein expression. Lpro and 3Cpro are viral proteinases that can cleave various host proteins and are responsible for several of the viral polyprotein cleavages. However, for the first time, we observed 2B-induced reduction of host protein. Further studies showed that 2B-mediated reduction of RIG-I is specific to FMDV, but not other picornaviruses, including encephalomyocarditis virus, enterovirus 71, and coxsackievirus A16. Moreover, we found the decreased protein level of RIG-I is independent of the cleavage of eukaryotic translation initiation factor 4 gamma, the induction of cellular apoptosis, or the association of proteasome, lysosome, and caspase pathways. A direct interaction was observed between RIG-I and 2B. The carboxyl-terminal amino acids 105 to 114 and amino acids 135 to 144 of 2B were essential for the reduction of RIG-I, while residues 105 to 114 were required for the interaction. These data suggest the antiviral role of RIG-I against FMDV and a novel antagonistic mechanism of FMDV that is mediated by 2B protein.IMPORTANCE This study demonstrated that RIG-I could suppress FMDV replication during virus infection. FMDV infection increased the transcriptional expression of RIG-I, while it decreased RIG-I protein expression. FMDV 2B protein interacted with RIG-I and induced reduction of RIG-I. 2B-induced reduction of RIG-I was independent of the induction of the cleavage of eukaryotic translation initiation factor 4 gamma or cellular apoptosis. In addition, proteasome, lysosome, and caspase pathways were not involved in this process. This study provides new insight into the immune evasion mediated by FMDV and identifies 2B as an antagonistic factor for FMDV to evade the antiviral response.

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“…The cells were purchased from the Cell Bank of Type Culture Collection of Chinese Academy of Sciences (Shanghai, China). Sendai virus (SeV), a model paramyxovirus routinely used to induce type I IFNs in cell culture, was obtained from Hongbing Shu's Laboratory (Wuhan University, China) (Li et al, 2016b;Zhou et al, 2014). FMDV O/BY/CHA/2010 (GenBank number: JN998085) and A/GDMM/CHA/2013 (GenBank number: KF450794) strains were used for virus infection.…”

Section: Cells Viruses and Antibodiesmentioning

confidence: 99%

“…The plasmid was verified by DNA sequencing analysis. The IFN-␤ promoter luciferase reporter plasmids and plasmids inserted with various HA-tagged genes (RIG-I(CARD), MDA5, VISA, TBK1, IRF3 and IRF7) used in this study were kindly provided by Professor Hongbing Shu (Wuhan University, China) (Li et al, 2016b;Zhou et al, 2014). As for the plasmids transfection, the Lipofectamine 2000 (Invitrogen) reagent was used according to the manufacture's protocol.…”

Section: Plasmids and Transfectionmentioning

confidence: 99%

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Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication

Zhu

Cao

et al. 2016

Molecular Immunology

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The VP3 structural protein of foot‐and‐mouth disease virus inhibits the IFN‐β signaling pathway

Cited by 71 publications

References 45 publications

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage

Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage

Foot-and-Mouth Disease Virus Viroporin 2B Antagonizes RIG-I-Mediated Antiviral Effects by Inhibition of Its Protein Expression

Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication

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