Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C Protein
Enterovirus A71 (EVA71) is a human enterovirus belonging to the Picornaviridae family and mostly causes hand-foot-and-mouth disease in infants. Viperin is an important interferon-stimulated gene with a broad antiviral activity against various viruses. However, the effect of viperin on human enterovi...
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MDPI AG
2018-12-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/11/1/13 |
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| author | Chunyu Wei Caishang Zheng Jianhong Sun Dan Luo Yan Tang Yuan Zhang Xianliang Ke Yan Liu Zhenhua Zheng Hanzhong Wang |
| author_facet | Chunyu Wei Caishang Zheng Jianhong Sun Dan Luo Yan Tang Yuan Zhang Xianliang Ke Yan Liu Zhenhua Zheng Hanzhong Wang |
| author_sort | Chunyu Wei |
| collection | DOAJ |
| description | Enterovirus A71 (EVA71) is a human enterovirus belonging to the Picornaviridae family and mostly causes hand-foot-and-mouth disease in infants. Viperin is an important interferon-stimulated gene with a broad antiviral activity against various viruses. However, the effect of viperin on human enteroviruses and the interaction mechanism between EVA71 and viperin remains elusive. Here, we confirmed the EVA71-induced expression of viperin in a mouse model and cell lines and showed that viperin upregulation by EVA71 infection occurred on both the mRNA and protein level. Viperin knockdown and overexpression in EVA71-infected cells indicated that this protein can markedly inhibit EVA71 infection. Interestingly, immunofluorescent confocal microscopy and co-immunoprecipitation assays indicated that viperin interacts and colocalizes with the EVA71 protein 2C in the endoplasmic reticulum. Furthermore, amino acids 50–60 in the N-terminal domain of viperin were the key residues responsible for viperin interaction with 2C. More importantly, the N-terminal domain of viperin was found responsible for inhibiting EVA71 replication. Our findings can potentially aid future research on the prevention and treatment of nervous system damage caused by EVA71 and may provide a potential target for antiviral therapy. |
| first_indexed | 2024-12-11T06:04:06Z |
| format | Article |
| id | doaj.art-3023cba250524876836c0e971e95ff73 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T06:04:06Z |
| publishDate | 2018-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-3023cba250524876836c0e971e95ff732022-12-22T01:18:22ZengMDPI AGViruses1999-49152018-12-011111310.3390/v11010013v11010013Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C ProteinChunyu Wei0Caishang Zheng1Jianhong Sun2Dan Luo3Yan Tang4Yuan Zhang5Xianliang Ke6Yan Liu7Zhenhua Zheng8Hanzhong Wang9CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaEnterovirus A71 (EVA71) is a human enterovirus belonging to the Picornaviridae family and mostly causes hand-foot-and-mouth disease in infants. Viperin is an important interferon-stimulated gene with a broad antiviral activity against various viruses. However, the effect of viperin on human enteroviruses and the interaction mechanism between EVA71 and viperin remains elusive. Here, we confirmed the EVA71-induced expression of viperin in a mouse model and cell lines and showed that viperin upregulation by EVA71 infection occurred on both the mRNA and protein level. Viperin knockdown and overexpression in EVA71-infected cells indicated that this protein can markedly inhibit EVA71 infection. Interestingly, immunofluorescent confocal microscopy and co-immunoprecipitation assays indicated that viperin interacts and colocalizes with the EVA71 protein 2C in the endoplasmic reticulum. Furthermore, amino acids 50–60 in the N-terminal domain of viperin were the key residues responsible for viperin interaction with 2C. More importantly, the N-terminal domain of viperin was found responsible for inhibiting EVA71 replication. Our findings can potentially aid future research on the prevention and treatment of nervous system damage caused by EVA71 and may provide a potential target for antiviral therapy.http://www.mdpi.com/1999-4915/11/1/13Enterovirus A71interferon-stimulated geneviperin2C proteinvirus-host interaction |
| spellingShingle | Chunyu Wei Caishang Zheng Jianhong Sun Dan Luo Yan Tang Yuan Zhang Xianliang Ke Yan Liu Zhenhua Zheng Hanzhong Wang Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C Protein Viruses Enterovirus A71 interferon-stimulated gene viperin 2C protein virus-host interaction |
| title | Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C Protein |
| title_full | Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C Protein |
| title_fullStr | Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C Protein |
| title_full_unstemmed | Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C Protein |
| title_short | Viperin Inhibits Enterovirus A71 Replication by Interacting with Viral 2C Protein |
| title_sort | viperin inhibits enterovirus a71 replication by interacting with viral 2c protein |
| topic | Enterovirus A71 interferon-stimulated gene viperin 2C protein virus-host interaction |
| url | http://www.mdpi.com/1999-4915/11/1/13 |
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