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

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.