H1N1 Influenza A Virus Protein NS2 Inhibits Innate Immune Response by Targeting IRF7

Bo Zhang; Minxuan Liu; Jiaxin Huang; Qiaoying Zeng; Qiyun Zhu; Shuai Xu; Hualan Chen

doi:10.3390/v14112411

H1N1 Influenza A Virus Protein NS2 Inhibits Innate Immune Response by Targeting IRF7

Viruses. 2022 Oct 31;14(11):2411. doi: 10.3390/v14112411.

Authors

Bo Zhang^{1

2}, Minxuan Liu^{1

2}, Jiaxin Huang^{1

2}, Qiaoying Zeng¹, Qiyun Zhu^{1

2}, Shuai Xu², Hualan Chen¹

Affiliations

¹ College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
² State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

Abstract

Influenza A virus (IAV) is a globally distributed zoonotic pathogen and causes a highly infectious respiratory disease with high morbidity and mortality in humans and animals. IAV has evolved various strategies to counteract the innate immune response, using different viral proteins. However, the mechanisms are not fully elucidated. In this study, we demonstrated that the nonstructural protein 2 (NS2) of H1N1 IAV negatively regulate the induction of type-I interferon. Co-immunoprecipitation experiments revealed that NS2 specifically interacts with interferon regulatory factor 7 (IRF7). NS2 blocks the nuclear translocation of IRF7 by inhibiting the formation of IRF7 dimers, thereby prevents the activation of IRF7 and inhibits the production of interferon-beta. Taken together, these findings revealed a novel mechanism by which the NS2 of H1N1 IAV inhibits IRF7-mediated type-I interferon production.

Keywords: influenza A virus; interferon; interferon regulatory factor 7; nonstructural protein 2.

Publication types

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

MeSH terms

Animals
Host-Pathogen Interactions
Humans
Immunity, Innate
Influenza A Virus, H1N1 Subtype* / metabolism
Influenza A virus* / physiology
Interferon Regulatory Factor-7 / genetics
Interferon Regulatory Factor-7 / metabolism
Interferon Type I* / metabolism
Viral Nonstructural Proteins / metabolism

Substances

Interferon Regulatory Factor-7
Interferon Type I
Viral Nonstructural Proteins

Grants and funding

This study was supported by funding from the National Key R&D program (2021YFD1800204), the National Natural Science Foundation of China (32172820, 31961133013, and 32272972), and the Chinese Academy of Agricultural Science and Technology Innovation Project (CAAS-ASTIP-JBGS-20210102).