Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation
Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) has led to significant economic losses in the global swine industry. Type I interferon (IFN-I) plays a crucial role in the host’s resistance to PRRSV infection. Despite extensive research showing that PRRSV employs multiple strateg...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s13567-024-01392-w |
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| author | Shuang-shuang Zhao Qisheng Qian Yao Wang Songlin Qiao Rui Li |
| author_facet | Shuang-shuang Zhao Qisheng Qian Yao Wang Songlin Qiao Rui Li |
| author_sort | Shuang-shuang Zhao |
| collection | DOAJ |
| description | Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) has led to significant economic losses in the global swine industry. Type I interferon (IFN-I) plays a crucial role in the host’s resistance to PRRSV infection. Despite extensive research showing that PRRSV employs multiple strategies to antagonise IFN-I induction, the underlying mechanisms remain to be fully elucidated. In this study, we have discovered that PRRSV inhibits the production of IFN-I by degrading TANK-binding kinase 1 (TBK1) through chaperon-mediated autophagy (CMA). From a mechanistic standpoint, PRRSV nonstructural protein 2 (Nsp2) increases the interaction between the heat shock protein member 8 (HSPA8) and TBK1. This interaction leads to the translocation of TBK1 into lysosomes for degradation, mediated by lysosomal-associated membrane protein 2A (LAMP2A). As a result, the downstream activation of IFN regulatory factor 3 (IRF3) and the production of IFN-I are hindered. Together, these results reveal a new mechanism by which PRRSV suppresses host innate immunity and contribute to the development of new antiviral strategies against the virus. |
| format | Article |
| id | doaj-art-c697a7962f2d4831be10d9b1c7d54f55 |
| institution | Kabale University |
| issn | 1297-9716 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-c697a7962f2d4831be10d9b1c7d54f552024-11-17T12:42:24ZengBMCVeterinary Research1297-97162024-11-0155111510.1186/s13567-024-01392-wPorcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferationShuang-shuang Zhao0Qisheng Qian1Yao Wang2Songlin Qiao3Rui Li4Key Laboratory of Applied Technology On Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology & College of Veterinary Medicine of Zhejiang A&F UniversityInstitute for Animal Health (Key Laboratory of Animal Immunology), Henan Academy of Agricultural SciencesInstitute for Animal Health (Key Laboratory of Animal Immunology), Henan Academy of Agricultural SciencesInstitute for Animal Health (Key Laboratory of Animal Immunology), Henan Academy of Agricultural SciencesInstitute for Animal Health (Key Laboratory of Animal Immunology), Henan Academy of Agricultural SciencesAbstract Porcine reproductive and respiratory syndrome virus (PRRSV) has led to significant economic losses in the global swine industry. Type I interferon (IFN-I) plays a crucial role in the host’s resistance to PRRSV infection. Despite extensive research showing that PRRSV employs multiple strategies to antagonise IFN-I induction, the underlying mechanisms remain to be fully elucidated. In this study, we have discovered that PRRSV inhibits the production of IFN-I by degrading TANK-binding kinase 1 (TBK1) through chaperon-mediated autophagy (CMA). From a mechanistic standpoint, PRRSV nonstructural protein 2 (Nsp2) increases the interaction between the heat shock protein member 8 (HSPA8) and TBK1. This interaction leads to the translocation of TBK1 into lysosomes for degradation, mediated by lysosomal-associated membrane protein 2A (LAMP2A). As a result, the downstream activation of IFN regulatory factor 3 (IRF3) and the production of IFN-I are hindered. Together, these results reveal a new mechanism by which PRRSV suppresses host innate immunity and contribute to the development of new antiviral strategies against the virus.https://doi.org/10.1186/s13567-024-01392-wPRRSVNsp2TBK1IFN-ICMA |
| spellingShingle | Shuang-shuang Zhao Qisheng Qian Yao Wang Songlin Qiao Rui Li Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation Veterinary Research PRRSV Nsp2 TBK1 IFN-I CMA |
| title | Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation |
| title_full | Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation |
| title_fullStr | Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation |
| title_full_unstemmed | Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation |
| title_short | Porcine reproductive and respiratory syndrome virus degrades TANK-binding kinase 1 via chaperon-mediated autophagy to suppress type I interferon production and facilitate viral proliferation |
| title_sort | porcine reproductive and respiratory syndrome virus degrades tank binding kinase 1 via chaperon mediated autophagy to suppress type i interferon production and facilitate viral proliferation |
| topic | PRRSV Nsp2 TBK1 IFN-I CMA |
| url | https://doi.org/10.1186/s13567-024-01392-w |
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