USP1 inhibits influenza A and B virus replication in MDCK cells by mediating RIG-I deubiquitination.

The post-translational modification and stability regulation of RIG-I play critical roles in promoting IFN-I production and maintaining immune homeostasis. In this study, we found that ubiquitin-specific peptidase 1 (USP1) promotes RIG-I protein stability through deubiquitination, which in turn enhances antiviral immunity through the production of inflammatory cytokines, and inhibits the replication of influenza virus in MDCK cells. In contrast, USP1 knockdown inhibited the deubiquitination of RIG-I, decreased the RIG-I protein level, and significantly increased the influenza virus titer. Meanwhile, inhibition of USP1 expression did not have a significant effect on the proliferation of MDCK cells, suggesting that USP1 could be used as a target gene to establish a vaccine-producing MDCK cell line. The above results provide a more comprehensive understanding of the function of USP1 and the antiviral response mechanism, and provide a theoretical and methodological basis for the screening of target genes for the artificial establishment of high-yield MDCK cell lines for vaccine production.