Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronaviruses
Pandemics of coronavirus (CoV)-related infection have been a major issue since the outbreaks of SARS, MERS and COVID-2019 in the past decades, leading a substantial threat to public health. Porcine deltacoronavirus (PDCoV), a new swine coronavirus, causes enteropathogenic disease characterized by ac...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2493922 |
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| author | Mingwei Li Yang Wu Jin Tian Qian Yang Mingze Gao Yongrui Wang Xuepeng Wang Ju Zhang Yudi Pan Hongyan Shi Da Shi Xin Zhang Jianfei Chen Longjun Guo Li Feng |
| author_facet | Mingwei Li Yang Wu Jin Tian Qian Yang Mingze Gao Yongrui Wang Xuepeng Wang Ju Zhang Yudi Pan Hongyan Shi Da Shi Xin Zhang Jianfei Chen Longjun Guo Li Feng |
| author_sort | Mingwei Li |
| collection | DOAJ |
| description | Pandemics of coronavirus (CoV)-related infection have been a major issue since the outbreaks of SARS, MERS and COVID-2019 in the past decades, leading a substantial threat to public health. Porcine deltacoronavirus (PDCoV), a new swine coronavirus, causes enteropathogenic disease characterized by acute diarrhoea, vomiting and dehydration in suckling piglets and poses potential risks of cross-species transmission. Here we reveal a novel function of CDC4 protein in restricting PDCoV infection. Ectopic expression of CDC4 suppresses PDCoV replication, whereas knockdown of CDC4 expression enhances PDCoV infection. Importantly, it was revealed that PDCoV encoded nucleocapsid (N) was involved in CDC4 nuclear-cytoplasmic shuttling, which was critical for CDC4 to exert the antiviral activity against PDCoV replication. Mechanistically, PDCoV N protein was detected to specifically interact with RIG-I to antagonize RIG-I-like receptor (RLR)-mediated IFN-β production, leading to disruptions of host innate immune defense. Meanwhile, CDC4 was proved to interact with PDCoV N protein and disrupted the interaction between PDCoV N and RIG-I, resulting in alleviated antagonism of IFN-β production mediated by PDCoV N. Similarly, a broad-spectrum inhibitory effects of CDC4 on N mediated antagonism were confirmed by the shared mechanisms among the different coronaviruses from Coronaviridae family, such as transmissible gastroenteritis virus (TGEV) from Alphacoronavirus (α-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Betacoronavirus (β-CoV). Therefore, a novel antiviral role of CDC4 was elucidated that CDC4 competes binding with CoVs N proteins to suppress CoVs N mediated antagonism of RLR associated signalling pathway in the context of diverse coronavirus infections. |
| format | Article |
| id | doaj-art-1c910925e05f48fd8ea39fa30d6a0414 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-1c910925e05f48fd8ea39fa30d6a04142025-08-20T02:15:58ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2493922Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronavirusesMingwei Li0Yang Wu1Jin Tian2Qian Yang3Mingze Gao4Yongrui Wang5Xuepeng Wang6Ju Zhang7Yudi Pan8Hongyan Shi9Da Shi10Xin Zhang11Jianfei Chen12Longjun Guo13Li Feng14State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaLaboratory of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaPandemics of coronavirus (CoV)-related infection have been a major issue since the outbreaks of SARS, MERS and COVID-2019 in the past decades, leading a substantial threat to public health. Porcine deltacoronavirus (PDCoV), a new swine coronavirus, causes enteropathogenic disease characterized by acute diarrhoea, vomiting and dehydration in suckling piglets and poses potential risks of cross-species transmission. Here we reveal a novel function of CDC4 protein in restricting PDCoV infection. Ectopic expression of CDC4 suppresses PDCoV replication, whereas knockdown of CDC4 expression enhances PDCoV infection. Importantly, it was revealed that PDCoV encoded nucleocapsid (N) was involved in CDC4 nuclear-cytoplasmic shuttling, which was critical for CDC4 to exert the antiviral activity against PDCoV replication. Mechanistically, PDCoV N protein was detected to specifically interact with RIG-I to antagonize RIG-I-like receptor (RLR)-mediated IFN-β production, leading to disruptions of host innate immune defense. Meanwhile, CDC4 was proved to interact with PDCoV N protein and disrupted the interaction between PDCoV N and RIG-I, resulting in alleviated antagonism of IFN-β production mediated by PDCoV N. Similarly, a broad-spectrum inhibitory effects of CDC4 on N mediated antagonism were confirmed by the shared mechanisms among the different coronaviruses from Coronaviridae family, such as transmissible gastroenteritis virus (TGEV) from Alphacoronavirus (α-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Betacoronavirus (β-CoV). Therefore, a novel antiviral role of CDC4 was elucidated that CDC4 competes binding with CoVs N proteins to suppress CoVs N mediated antagonism of RLR associated signalling pathway in the context of diverse coronavirus infections.https://www.tandfonline.com/doi/10.1080/22221751.2025.2493922CoronavirusCDC4nuclear shuttlingbroad-spectrumantiviral activity |
| spellingShingle | Mingwei Li Yang Wu Jin Tian Qian Yang Mingze Gao Yongrui Wang Xuepeng Wang Ju Zhang Yudi Pan Hongyan Shi Da Shi Xin Zhang Jianfei Chen Longjun Guo Li Feng Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronaviruses Emerging Microbes and Infections Coronavirus CDC4 nuclear shuttling broad-spectrum antiviral activity |
| title | Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronaviruses |
| title_full | Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronaviruses |
| title_fullStr | Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronaviruses |
| title_full_unstemmed | Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronaviruses |
| title_short | Nuclear shuttling of CDC4 mediated broad-spectrum antiviral activity against diverse coronaviruses |
| title_sort | nuclear shuttling of cdc4 mediated broad spectrum antiviral activity against diverse coronaviruses |
| topic | Coronavirus CDC4 nuclear shuttling broad-spectrum antiviral activity |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2025.2493922 |
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