The host protein CALCOCO2 interacts with bovine viral diarrhoea virus Npro, inhibiting type I interferon production and thereby promoting viral replication
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Virulence - 15(2023), 1 vom: 21. Dez., Seite 2289764 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Song [VerfasserIn] |
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| Links: |
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| Themen: |
BVDV |
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| Anmerkungen: |
Date Completed 05.12.2023 Date Revised 21.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/21505594.2023.2289764 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365386944 |
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| 245 | 1 | 4 | |a The host protein CALCOCO2 interacts with bovine viral diarrhoea virus Npro, inhibiting type I interferon production and thereby promoting viral replication |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Npro | |
| 650 | 4 | |a innate immunity | |
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| 700 | 1 | |a Wei, Ran |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xiaomei |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Aizaz, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fangxu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hongmei |e verfasserin |4 aut | |
| 700 | 1 | |a He, Hongbin |e verfasserin |4 aut | |
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