Guanylate-Binding Protein 1, an Interferon-Induced GTPase, Exerts an Antiviral Activity against Classical Swine Fever Virus Depending on Its GTPase Activity.
Bottom Line: In addition, we found that GBP1 was upregulated at the transcriptional level in CSFV-infected PK-15 cells and in various organs of CSFV-infected pigs.We showed further that the NS5A-GBP1 interaction inhibited GTPase activity, which was critical for its antiviral effect.The K51 of GBP1, critical for its GTPase activity, is essential for the antiviral action of GBP1 against CSFV replication, and the binding of the NS5A protein to GBP1 antagonizes the GTPase activity and thus the antiviral effect.
Affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.Show MeSH
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Mentions: It has been reported that the expression levels of several ISGs affect the functions of various cellular signaling pathways to exert antiviral activity (25). For instance, GBP1 shows inhibitory effects on dengue virus (DENV) infection by influencing the activity of NF-κB (34). OASL binds directly to RIG-I and positively regulates the expression of IFN-β and ISGs (35). To examine whether GBP1 affects the functions of various cellular signaling pathways, the luciferase activities of lysates from cells transfected with the luciferase reporters driven by IFN-β, interferon-stimulated response element (ISRE), or NF-κB promoters were measured. The results revealed that GBP1 overexpression did not enhance luciferase activities relative to those of empty vector-transfected cells with or without SeV treatment, suggesting that GBP1 does not activate IFN-β, ISRE, or NF-κB promoter activity. The results indicated that GBP1 did not trigger the IFN-β (Fig. 4A), ISRE (Fig. 4B), or NF-κB (Fig. 4C) pathway.
Affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.