Nonstructural protein 1 of influenza A virus interacts with human guanylate-binding protein 1 to antagonize antiviral activity

Zixiang Zhu; Zixue Shi; Wenjun Yan; Jianchao Wei; Donghua Shao; Xufang Deng; Shaohui Wang; Beibei Li; Guangzhi Tong; Zhiyong Ma

doi:10.1371/journal.pone.0055920

Nonstructural protein 1 of influenza A virus interacts with human guanylate-binding protein 1 to antagonize antiviral activity

PLoS One. 2013;8(2):e55920. doi: 10.1371/journal.pone.0055920. Epub 2013 Feb 6.

Authors

Zixiang Zhu¹, Zixue Shi, Wenjun Yan, Jianchao Wei, Donghua Shao, Xufang Deng, Shaohui Wang, Beibei Li, Guangzhi Tong, Zhiyong Ma

Affiliation

¹ Department of Veterinary Public Health, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents*
Blotting, Western
Dogs
Fluorescent Antibody Technique
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism*
Host-Pathogen Interactions*
Humans
Immunoprecipitation
Influenza A virus / metabolism
Influenza A virus / pathogenicity*
Influenza, Human / genetics
Influenza, Human / metabolism
Influenza, Human / virology*
Madin Darby Canine Kidney Cells
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins / metabolism*
Virus Replication*

Substances

Antiviral Agents
GBP1 protein, human
INS1 protein, influenza virus
RNA, Messenger
Viral Nonstructural Proteins
GTP-Binding Proteins

Grants and funding

This work was sponsored by the National Natural Science Foundation of China (no. 30970141 and no. 81171547) and the Natural Science Foundation of Shanghai (no. 10JC1417300). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.