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: To map the region of GBP1 required for binding to NS5A, we constructed two plasmids expressing Flag-tagged truncated mutants of GBP1, i.e., GBP1(1-308) and GBP1(309-591) (20) (Fig. 7A and B). These plasmids were cotransfected with pMyc-NS5A into HEK293T cells and subjected to the co-IP assay. The results showed that NS5A interacted with GBP1 and GBP1(1-308) but not with GBP1(309-591) (Fig. 7C). These findings indicate that the N-terminal globular GTPase domain of GBP1 is critical for the NS5A-GBP1 interaction.
Affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.