Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

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

doi:10.1038/srep21888

Cited by 58 publications

(57 citation statements)

References 49 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: 59%

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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: 59%

“…As a result, IFN production and signal transduction are suppressed. FMDV infection restricts the expression of RIG-I, DMA5, and MAVS to attenuate host innate immune responses (18,27,29). FMDV can also target NEMO to cleave it to inhibit NF-B-and IRF3-mediated IFN production (30).…”

Section: Discussionmentioning

confidence: 99%

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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“…3A protein has been identified as a negative regulator of virus-triggered IFN-β signaling pathway (Li et al, 2016a). Overexpression of 3A inhibited SeV-triggered activation of IRF3 and the expression of RIG-I/MDA5 in HEK293T and PK15 cells.…”

Section: Fmdv Interference With Innate Antiviral Responsesmentioning

confidence: 99%

Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response

Pulido

Sáiz

2017

Front. Cell. Infect. Microbiol.

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Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

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“…FMDV infection also results in reduction of MAVS, but not through its cleavage. Instead, the non-structural protein, 3A, and structural protein, VP3, have both been shown to down-regulate MAVS mRNA expression [48,49]. …”

Section: Interferon (Ifn)-induced Viral Rna (Vrna) Degradationmentioning

confidence: 99%

Diverse Strategies Used by Picornaviruses to Escape Host RNA Decay Pathways

Ullmer

Semler

2016

Viruses

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To successfully replicate, viruses protect their genomic material from degradation by the host cell. RNA viruses must contend with numerous destabilizing host cell processes including mRNA decay pathways and viral RNA (vRNA) degradation resulting from the antiviral response. Members of the Picornaviridae family of small RNA viruses have evolved numerous diverse strategies to evade RNA decay, including incorporation of stabilizing elements into vRNA and re-purposing host stability factors. Viral proteins are deployed to disrupt and inhibit components of the decay machinery and to redirect decay machinery to the advantage of the virus. This review summarizes documented interactions of picornaviruses with cellular RNA decay pathways and processes.

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Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

Cited by 58 publications

References 49 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

Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response

Diverse Strategies Used by Picornaviruses to Escape Host RNA Decay Pathways

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