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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
BMC biology
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40691603/ |
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| _version_ | 1868266174432673793 |
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| author | Qin, Zhiran Xie, Xiaoting Ye, Hua Wu, Hao Li, Zhuoyun Li, Jingshu He, Xiaoen Liang, Zuxin Liu, Xuling Zhu, Li Wu, Qinghua Xiao, Weiwei Wu, Kefeng Wan, Chengsong Zhang, Bao Sun, Zhaohui Yu, Jianhai Shen, Chenguang Yu, Linzhong Zhao, Wei |
| author_facet | Qin, Zhiran Xie, Xiaoting Ye, Hua Wu, Hao Li, Zhuoyun Li, Jingshu He, Xiaoen Liang, Zuxin Liu, Xuling Zhu, Li Wu, Qinghua Xiao, Weiwei Wu, Kefeng Wan, Chengsong Zhang, Bao Sun, Zhaohui Yu, Jianhai Shen, Chenguang Yu, Linzhong Zhao, Wei Qin, Zhiran Xie, Xiaoting Ye, Hua Wu, Hao Li, Zhuoyun Li, Jingshu He, Xiaoen Liang, Zuxin Liu, Xuling Zhu, Li Wu, Qinghua Xiao, Weiwei Wu, Kefeng Wan, Chengsong Zhang, Bao Sun, Zhaohui Yu, Jianhai Shen, Chenguang Yu, Linzhong Zhao, Wei |
| collection | PubMed - marine biology |
| contents | A lethal DENV-2 wild-type mouse model for mutagenesis investigations. Qin, Zhiran Xie, Xiaoting Ye, Hua Wu, Hao Li, Zhuoyun Li, Jingshu He, Xiaoen Liang, Zuxin Liu, Xuling Zhu, Li Wu, Qinghua Xiao, Weiwei Wu, Kefeng Wan, Chengsong Zhang, Bao Sun, Zhaohui Yu, Jianhai Shen, Chenguang Yu, Linzhong Zhao, Wei Humans Animals Mice Mice, Inbred C57BL Mutagenesis Dengue Virus Disease Models, Animal Dengue Viral Nonstructural Proteins Mutation Zika Virus Zika Virus Infection Viremia Genes, Lethal Cells, Cultured Effective mouse models for testing antiviral medications should be both cost-effective and require minimal labor. Immunodeficient mouse models, such as AG129, are commonly used in dengue virus (DENV) research; however, their high import and maintenance costs make them relatively expensive. Moreover, the absence of IFN-γ signaling limits the capacity of the AG129 model. To date, wild-type mouse models of DENV infection have only exhibited mild symptoms without lethality, limiting their research applicability. In this study, we developed a lethal C57BL/6 wild-type mouse model infected with DENV-2 365 strain. By blocking the type I interferon receptor before the virus challenge, we allowed the immune response to be restored at a later stage of infection. Following infection, the mice exhibited severe symptoms, including weight loss, high viremia levels, elevated inflammatory cytokines, significant vascular leakage, and pathological changes in the brain, kidney, liver and spleen. The model also displayed severe central nervous symptoms and 100% mortality. Additionally, we used this model to evaluate an adaptable NS2A protein mutation found in both Zika virus and DENV-2. Our study introduces an alternative model design for investigating viral mutations, providing a valuable tool for future research. |
| format | Artículo científico |
| id | pubmed_40691603 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | BMC biology |
| record_format | pubmed |
| spellingShingle | A lethal DENV-2 wild-type mouse model for mutagenesis investigations. Qin, Zhiran Xie, Xiaoting Ye, Hua Wu, Hao Li, Zhuoyun Li, Jingshu He, Xiaoen Liang, Zuxin Liu, Xuling Zhu, Li Wu, Qinghua Xiao, Weiwei Wu, Kefeng Wan, Chengsong Zhang, Bao Sun, Zhaohui Yu, Jianhai Shen, Chenguang Yu, Linzhong Zhao, Wei Humans Animals Mice Mice, Inbred C57BL Mutagenesis Dengue Virus Disease Models, Animal Dengue Viral Nonstructural Proteins Mutation Zika Virus Zika Virus Infection Viremia Genes, Lethal Cells, Cultured A lethal DENV-2 wild-type mouse model for mutagenesis investigations. Qin, Zhiran Xie, Xiaoting Ye, Hua Wu, Hao Li, Zhuoyun Li, Jingshu He, Xiaoen Liang, Zuxin Liu, Xuling Zhu, Li Wu, Qinghua Xiao, Weiwei Wu, Kefeng Wan, Chengsong Zhang, Bao Sun, Zhaohui Yu, Jianhai Shen, Chenguang Yu, Linzhong Zhao, Wei Humans Animals Mice Mice, Inbred C57BL Mutagenesis Dengue Virus Disease Models, Animal Dengue Viral Nonstructural Proteins Mutation Zika Virus Zika Virus Infection Viremia Genes, Lethal Cells, Cultured Effective mouse models for testing antiviral medications should be both cost-effective and require minimal labor. Immunodeficient mouse models, such as AG129, are commonly used in dengue virus (DENV) research; however, their high import and maintenance costs make them relatively expensive. Moreover, the absence of IFN-γ signaling limits the capacity of the AG129 model. To date, wild-type mouse models of DENV infection have only exhibited mild symptoms without lethality, limiting their research applicability. In this study, we developed a lethal C57BL/6 wild-type mouse model infected with DENV-2 365 strain. By blocking the type I interferon receptor before the virus challenge, we allowed the immune response to be restored at a later stage of infection. Following infection, the mice exhibited severe symptoms, including weight loss, high viremia levels, elevated inflammatory cytokines, significant vascular leakage, and pathological changes in the brain, kidney, liver and spleen. The model also displayed severe central nervous symptoms and 100% mortality. Additionally, we used this model to evaluate an adaptable NS2A protein mutation found in both Zika virus and DENV-2. Our study introduces an alternative model design for investigating viral mutations, providing a valuable tool for future research. |
| title | A lethal DENV-2 wild-type mouse model for mutagenesis investigations. |
| topic | Humans Animals Mice Mice, Inbred C57BL Mutagenesis Dengue Virus Disease Models, Animal Dengue Viral Nonstructural Proteins Mutation Zika Virus Zika Virus Infection Viremia Genes, Lethal Cells, Cultured |
| url | https://pubmed.ncbi.nlm.nih.gov/40691603/ |