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The host protein CALCOCO2 interacts with bovine viral diarrhoea virus Npro, inhibiting type I interferon production and thereby promoting viral replication.
- Source :
-
Virulence [Virulence] 2024 Dec; Vol. 15 (1), pp. 2289764. Date of Electronic Publication: 2023 Dec 04. - Publication Year :
- 2024
-
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.
Details
- Language :
- English
- ISSN :
- 2150-5608
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Virulence
- Publication Type :
- Academic Journal
- Accession number :
- 38047736
- Full Text :
- https://doi.org/10.1080/21505594.2023.2289764