Foot-and-Mouth Disease Virus 3A Protein Causes Upregulation of Autophagy-Related Protein LRRC25 To Inhibit the G3BP1-Mediated RIG-Like Helicase-Signaling Pathway.
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ABSTRACT: Foot-and-mouth disease virus (FMDV) is one of the most notorious pathogens in the global livestock industry. To establish an infection, FMDV needs to counteract host antiviral responses. Several studies have shown how FMDV suppresses the type I interferon (IFN) response; however, whether FMDV modulates the integrated autophagy and innate immunity remains largely unknown. Here, the porcine Ras-GAP SH3-binding protein 1 (G3BP1) was shown to promote the retinoic acid-inducible gene I (RIG-I)-like helicase (RLH) signaling by upregulating the expression of RIG-I and melanoma differentiation-associated gene 5 (MDA5). FMDV nonstructural protein 3A interacted with G3BP1 to inhibit G3BP1 expression and G3BP1-mediated RLH signaling by upregulating the expression of autophagy-related protein LRRC25. In addition, 3A proteins of other picornaviruses, including Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also showed similar actions. Taking the data together, we elucidated, for the first time, a novel mechanism by which FMDV has evolved to inhibit IFN signaling and counteract host innate antiviral responses by autophagy.IMPORTANCE We show that foot-and-mouth disease virus (FMDV) 3A inhibits retinoic acid-inducible gene I (RIG-I)-like helicase signaling by degrading G3BP1 protein. Furthermore, FMDV 3A reduces G3BP1 by upregulating the expression of autophagy-related protein LRRC25. Additionally, other picornavirus 3A proteins, such as Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also degrade G3BP1 by upregulating LRRC25 expression. This study will help us improve the design of current vaccines and aid the development of novel control strategies to combat FMD.
SUBMITTER: Yang W
PROVIDER: S-EPMC7108857 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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