Hongyang Liu，Guangqiang Ye，Xiaohong Liu，Mengdi Xue，Qiongqiong Zhou，Longfeng Zhang，Kunli Zhang，Li Huang，Changjiang Weng

Cell Rep.2022 Oct 11;41(2):111469.doi: 10.1016/j.celrep.2022.111469.

Abstract

Cytoskeleton proteins have been reported to be involved in the host antiviral immune responses. However, how cytoskeleton proteins regulate host antiviral immune responses is not fully understood. Here we report that the cytoskeletal protein vimentin is a negative regulator of type I interferon (IFN-I) production upon viral infection. Ectopic expression of vimentin suppresses RNA- and DNA viruses-induced IFN-I production, whereas knockout of vimentin expression enhances IFN-I production. Viral infection increases vimentin expression and ultimately inhibits IFN-I production. Mechanistically, upregulated vimentin interacts with TBK1 and IKKε to disrupt the interactions of TBK1-IRF3 and IKKε-IRF3, resulting in inhibition of IRF3 phosphorylation and nuclear translocation. Furthermore, we generate vimentin knockout mice to confirm that deficiency of vimentin gene in mice suppressed encephalomyocarditis virus replication in vivo. Our findings demonstrates that vimentin plays an important role in regulating IFN-I production, revealing its antiviral function of the cytoskeletal protein vimentin.

Keywords: CP: Immunology; TBK1-IKKε-IRF3 axis; interferon; knockout mice; vimentin.