Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response
Diseases caused by viruses threaten the production industry and food safety of aquaculture which is a great animal protein source. Grass carp reovirus (GCRV) has caused tremendous loss, and the molecular function of viral proteins during infection needs further research, as for most aquatic viruses....
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MDPI AG
2020-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/4/560 |
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| author | Hang Su Chengjian Fan Zhiwei Liao Chunrong Yang Jihong Liu Clarke Yongan Zhang Jianguo Su |
| author_facet | Hang Su Chengjian Fan Zhiwei Liao Chunrong Yang Jihong Liu Clarke Yongan Zhang Jianguo Su |
| author_sort | Hang Su |
| collection | DOAJ |
| description | Diseases caused by viruses threaten the production industry and food safety of aquaculture which is a great animal protein source. Grass carp reovirus (GCRV) has caused tremendous loss, and the molecular function of viral proteins during infection needs further research, as for most aquatic viruses. In this study, interaction between GCRV major outer capsid protein VP4 and RIG-I, a critical viral RNA sensor, was screened out by GST pull-down, endogenous immunoprecipitation and subsequent LC-MS/MS, and then verified by co-IP and an advanced far-red fluorescence complementation system. VP4 was proved to bind to the CARD and RD domains of RIG-I and promoted K48-linked ubiquitination of RIG-I to degrade RIG-I. VP4 reduced mRNA and promoter activities of key genes of RLR pathway and sequential IFN production. As a consequence, antiviral effectors were suppressed and GCRV replication increased, resulting in intensified cytopathic effect. Furthermore, results of transcriptome sequencing of VP4 stably expressed CIK (<i>C. idella</i> kidney) cells indicated that VP4 activated the MyD88-dependent TLR pathway. Knockdown of VP4 obtained opposite effects. These results collectively revealed that VP4 interacts with RIG-I to restrain interferon response and assist GCRV invasion. This study lays the foundation for anti-dsRNA virus molecular function research in teleost and provides a novel insight into the strategy of immune evasion for aquatic virus. |
| first_indexed | 2024-03-10T20:39:20Z |
| format | Article |
| id | doaj.art-e7c3f0ceb12f4071b813b649946cad85 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:39:20Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e7c3f0ceb12f4071b813b649946cad852023-11-19T20:49:47ZengMDPI AGBiomolecules2218-273X2020-04-0110456010.3390/biom10040560Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon ResponseHang Su0Chengjian Fan1Zhiwei Liao2Chunrong Yang3Jihong Liu Clarke4Yongan Zhang5Jianguo Su6Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Veterinary Medicine, Huazhong Agricultural University, Wuhan,430070, ChinaNorwegian Institute for Bioeconomy Research, 1430 Ås, NorwayDepartment of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaDiseases caused by viruses threaten the production industry and food safety of aquaculture which is a great animal protein source. Grass carp reovirus (GCRV) has caused tremendous loss, and the molecular function of viral proteins during infection needs further research, as for most aquatic viruses. In this study, interaction between GCRV major outer capsid protein VP4 and RIG-I, a critical viral RNA sensor, was screened out by GST pull-down, endogenous immunoprecipitation and subsequent LC-MS/MS, and then verified by co-IP and an advanced far-red fluorescence complementation system. VP4 was proved to bind to the CARD and RD domains of RIG-I and promoted K48-linked ubiquitination of RIG-I to degrade RIG-I. VP4 reduced mRNA and promoter activities of key genes of RLR pathway and sequential IFN production. As a consequence, antiviral effectors were suppressed and GCRV replication increased, resulting in intensified cytopathic effect. Furthermore, results of transcriptome sequencing of VP4 stably expressed CIK (<i>C. idella</i> kidney) cells indicated that VP4 activated the MyD88-dependent TLR pathway. Knockdown of VP4 obtained opposite effects. These results collectively revealed that VP4 interacts with RIG-I to restrain interferon response and assist GCRV invasion. This study lays the foundation for anti-dsRNA virus molecular function research in teleost and provides a novel insight into the strategy of immune evasion for aquatic virus.https://www.mdpi.com/2218-273X/10/4/560grass carp reovirus (GCRV)major outer capsid protein VP4molecular functionhost/pathogen protein interactionRIG-I-like receptor signaling pathwayimmune evasion |
| spellingShingle | Hang Su Chengjian Fan Zhiwei Liao Chunrong Yang Jihong Liu Clarke Yongan Zhang Jianguo Su Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response Biomolecules grass carp reovirus (GCRV) major outer capsid protein VP4 molecular function host/pathogen protein interaction RIG-I-like receptor signaling pathway immune evasion |
| title | Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response |
| title_full | Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response |
| title_fullStr | Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response |
| title_full_unstemmed | Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response |
| title_short | Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response |
| title_sort | grass carp reovirus major outer capsid protein vp4 interacts with rna sensor rig i to suppress interferon response |
| topic | grass carp reovirus (GCRV) major outer capsid protein VP4 molecular function host/pathogen protein interaction RIG-I-like receptor signaling pathway immune evasion |
| url | https://www.mdpi.com/2218-273X/10/4/560 |
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