Abstract
ABSTRACT Bovine viral diarrhoea-mucosal disease caused by bovine viral diarrhoea virus (BVDV) is a major infectious disease that affects the cattle industry. The nonstructural protein Npro of BVDV antagonizes the type I interferon (IFN-I) pathway, thereby escaping the host immune response. The exact mechanism by which Npro uses host proteins to inhibit IFN-I production is unclear. The host protein CALCOCO2 was identified as a binding partner of Npro using a yeast two-hybrid screen. The interaction between Npro and CALCOCO2 was confirmed by yeast co-transformation, co-immunoprecipitation assays, and GST pull-down assays. The stable overexpression of CALCOCO2 markedly promoted BVDV propagation, while the knockdown of CALCOCO2 significantly inhibited BVDV replication in MDBK cells. Interestingly, CALCOCO2 inhibited IFN-I and IFN-stimulated gene production in BVDV-infected cells. Ectopic expression of CALCOCO2 effectively reduced IRF3 protein levels via the proteasome pathway. CALCOCO2 was found to promote Npro-mediated ubiquitination degradation of IRF3 by interacting with IRF3. Our results demonstrate the molecular mechanism by which Npro recruits the CALCOCO2 protein to regulate IRF3 degradation to inhibit IFN-I production.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
