Zhang Huan, Jiang Pengfei, Chen Zeliang, Wang Dang, Zhou Yanrong, Zhu Xinyu, Xiao Shaobo, Fang Liurong
Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Shenyang, 110866, China.
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.
Virology. 2022 Jun;571:12-20. doi: 10.1016/j.virol.2022.04.004. Epub 2022 Apr 12.
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-mediated cleavage of NEMO and this cleavage suppresses the ability of NEMO to activate downstream IFN production. These findings demonstrate that NoV3CL-induced cleavage limits NEMO to the activation of type I IFN signaling. In summary, our findings indicate that NoV3CL is a new interferon antagonist, and enhances our understanding of the escape of innate immunity mediated by NoV3CL.
诺如病毒（NoV）引起的疫情最近在全球范围内爆发。诺如病毒严重病例可导致患者死亡，引发重大公共卫生问题。在感染初期，对抗宿主干扰素（IFN）的产生是病毒建立感染的重要策略。然而，诺如病毒与干扰素之间的关系及其机制仍不清楚。在本研究中，发现诺如病毒编码的3C样蛋白酶通过切割NF-κB必需调节因子（NEMO）有效抑制仙台病毒（SEV）介导的IFN-β产生。谷氨酰胺205是诺如病毒3C样蛋白酶介导的NEMO切割位点，这种切割抑制了NEMO激活下游IFN产生的能力。这些发现表明，诺如病毒3C样蛋白酶诱导的切割限制了NEMO对I型IFN信号的激活。总之，我们的研究结果表明，诺如病毒3C样蛋白酶是一种新的干扰素拮抗剂，并增强了我们对诺如病毒3C样蛋白酶介导的先天免疫逃逸的理解。
