title: Nonstructural protein 1 of influenza A virus interacts with human guanylate-binding protein 1 to antagonize antiviral activity.
abstract: Human guanylate-binding protein 1 (hGBP1) is an interferon-inducible protein involved in the host immune response against viral infection. In response to infection by influenza A virus (IAV), hGBP1 transcript and protein were significantly upregulated. Overexpression of hGBP1 inhibited IAV replication in a dose-dependent manner in vitro. The lysine residue at position 51 (K51) of hGBP1 was essential for inhibition of IAV replication. Mutation of K51 resulted in an hGBP1 that was unable to inhibit IAV replication. The viral nonstructural protein 1 (NS1) was found to interact directly with hGBP1. K51 of hGBP1 and a region between residues 123 and 144 in NS1 were demonstrated to be essential for the interaction between NS1 and hGBP1. Binding of NS1 to hGBP1 resulted in a significant reduction in both GTPase activity and the anti-IAV activity of hGBP1. These findings indicated that hGBP1 contributed to the host immune response against IAV replication and that hGBP1-mediated antiviral activity was antagonized by NS1 via binding to hGBP1.
authors: Department of Veterinary Public Health, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors: Zixiang
authors: Z
authors: Zhu
authors: Zixue
authors: Z
authors: Shi
authors: Wenjun
authors: W
authors: Yan
authors: Jianchao
authors: J
authors: Wei
authors: Donghua
authors: D
authors: Shao
authors: Xufang
authors: X
authors: Deng
authors: Shaohui
authors: S
authors: Wang
authors: Beibei
authors: B
authors: Li
authors: Guangzhi
authors: G
authors: Tong
authors: Zhiyong
authors: Z
authors: Ma
mesh_terms: D000818:Animals; D000998:Antiviral Agents; D015153:Blotting, Western; D004285:Dogs; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D009980:Influenza A virus / Q000378:metabolism / Q000472:pathogenicity*; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; C490287:GBP1 protein, human; C085820:INS1 protein, influenza virus; D012333:RNA, Messenger; D017361:Viral Nonstructural Proteins; D019204:GTP-Binding Proteins