Norovirus 3C-Like protease antagonizes interferon-β production by cleaving NEMO

Huan Zhang; Pengfei Jiang; Zeliang Chen; Dang Wang; Yanrong Zhou; Xinyu Zhu; Shaobo Xiao; Liurong Fang

doi:10.1016/j.virol.2022.04.004

Norovirus 3C-Like protease antagonizes interferon-β production by cleaving NEMO

Virology. 2022 Jun:571:12-20. doi: 10.1016/j.virol.2022.04.004. Epub 2022 Apr 12.

Authors

Huan Zhang¹, Pengfei Jiang¹, Zeliang Chen¹, Dang Wang², Yanrong Zhou², Xinyu Zhu², Shaobo Xiao², Liurong Fang³

Affiliations

¹ Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Shenyang, 110866, China.
² State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China.
³ State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. Electronic address: fanglr@mail.hzau.edu.cn.

PMID: 35436639
DOI: 10.1016/j.virol.2022.04.004

Abstract

An epidemic owing to Norovirus (NoV) has recently been occurring worldwide. Severe cases of NoV can lead to patient death, resulting in significant public health problems. In the early stages of infection, antagonizing the production of host interferon (IFN) is an important strategy for viruses to establish infection. However, the relationship between NoV and interferon and its mechanism remains unclear. In this study, the 3C-like protease encoded by NoV was found to effectively suppress Sendai virus (SEV)-mediated IFN-β production by cleaving the NF-κB essential modulator (NEMO). Glutamine 205 is the site of NoV3CL^pro-mediated cleavage of NEMO and this cleavage suppresses the ability of NEMO to activate downstream IFN production. These findings demonstrate that NoV3CL^pro-induced cleavage limits NEMO to the activation of type I IFN signaling. In summary, our findings indicate that NoV3CL^pro is a new interferon antagonist, and enhances our understanding of the escape of innate immunity mediated by NoV3CL^pro.

Keywords: 3C-like protease; Interferon-β; NEMO; Norovirus.

Publication types

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

MeSH terms

Antiviral Agents
Cysteine Endopeptidases
Humans
Interferon-beta / genetics
Interferons / genetics
Norovirus* / genetics
Peptide Hydrolases*

Substances

Antiviral Agents
Interferon-beta
Interferons
Peptide Hydrolases
Cysteine Endopeptidases