TRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradation
Abstract Background Recognition of viral invasion by innate antiviral immune system triggers activation of the type I interferon (IFN-I) and proinflammatory signaling pathways. Subsequently, IFN-I induction regulates expression of a group of genes known as IFN-I-stimulated genes (ISGs) to block vira...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-022-00872-w |
| _version_ | 1811274852673257472 |
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| author | Shulong Zu Chunfeng Li Lili Li Yong-Qiang Deng Xiang Chen Dan Luo Qing Ye Yi-Jiao Huang Xiao-Feng Li Rong-Rong Zhang Nina Sun Xianqi Zhang Saba R. Aliyari Karin Nielsen-Saines Jae U. Jung Heng Yang Cheng-Feng Qin Genhong Cheng |
| author_facet | Shulong Zu Chunfeng Li Lili Li Yong-Qiang Deng Xiang Chen Dan Luo Qing Ye Yi-Jiao Huang Xiao-Feng Li Rong-Rong Zhang Nina Sun Xianqi Zhang Saba R. Aliyari Karin Nielsen-Saines Jae U. Jung Heng Yang Cheng-Feng Qin Genhong Cheng |
| author_sort | Shulong Zu |
| collection | DOAJ |
| description | Abstract Background Recognition of viral invasion by innate antiviral immune system triggers activation of the type I interferon (IFN-I) and proinflammatory signaling pathways. Subsequently, IFN-I induction regulates expression of a group of genes known as IFN-I-stimulated genes (ISGs) to block viral infection. The tripartite motif containing 22 (TRIM22) is an ISG with strong antiviral functions. Results Here we have shown that the TRIM22 has been strongly upregulated both transcriptionally and translationally upon Zika virus (ZIKV) infection. ZIKV infection is associated with a wide range of clinical manifestations in human from mild to severe symptoms including abnormal fetal brain development. We found that the antiviral function of TRIM22 plays a crucial role in counterattacking ZIKV infection. Overexpression of TRIM22 protein inhibited ZIKV growth whereas deletion of TRIM22 in host cells increased ZIKV infectivity. Mechanistically, TRIM22, as a functional E3 ubiquitin ligase, promoted the ubiquitination and degradation of ZIKV nonstructural protein 1 (NS1) and nonstructural protein 3 (NS3). Further studies showed that the SPRY domain and Ring domain of TRIM22 played important roles in protein interaction and degradation, respectively. In addition, we found that TRIM22 also inhibited other flaviviruses infection including dengue virus (DENV) and yellow fever virus (YFV). Conclusion Thus, TRIM22 is an ISG with important role in host defense against flaviviruses through binding and degradation of the NS1 and NS3 proteins. |
| first_indexed | 2024-04-12T23:27:37Z |
| format | Article |
| id | doaj.art-f43bbfb19fd944599b448e81b526f689 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-12T23:27:37Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-f43bbfb19fd944599b448e81b526f6892022-12-22T03:12:23ZengBMCCell & Bioscience2045-37012022-08-0112111210.1186/s13578-022-00872-wTRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradationShulong Zu0Chunfeng Li1Lili Li2Yong-Qiang Deng3Xiang Chen4Dan Luo5Qing Ye6Yi-Jiao Huang7Xiao-Feng Li8Rong-Rong Zhang9Nina Sun10Xianqi Zhang11Saba R. Aliyari12Karin Nielsen-Saines13Jae U. Jung14Heng Yang15Cheng-Feng Qin16Genhong Cheng17Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford UniversityInstitute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical CollegeCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Microbiology, Immunology and Molecular Genetics, University of CaliforniaDivision of Pediatric Infectious Diseases, David Geffen School of Medicine, University of CaliforniaDepartment of Cancer Biology and Global Center for Pathogens Research and Human Health, Lerner Research Institute, Cleveland ClinicInstitute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical SciencesDepartment of Microbiology, Immunology and Molecular Genetics, University of CaliforniaAbstract Background Recognition of viral invasion by innate antiviral immune system triggers activation of the type I interferon (IFN-I) and proinflammatory signaling pathways. Subsequently, IFN-I induction regulates expression of a group of genes known as IFN-I-stimulated genes (ISGs) to block viral infection. The tripartite motif containing 22 (TRIM22) is an ISG with strong antiviral functions. Results Here we have shown that the TRIM22 has been strongly upregulated both transcriptionally and translationally upon Zika virus (ZIKV) infection. ZIKV infection is associated with a wide range of clinical manifestations in human from mild to severe symptoms including abnormal fetal brain development. We found that the antiviral function of TRIM22 plays a crucial role in counterattacking ZIKV infection. Overexpression of TRIM22 protein inhibited ZIKV growth whereas deletion of TRIM22 in host cells increased ZIKV infectivity. Mechanistically, TRIM22, as a functional E3 ubiquitin ligase, promoted the ubiquitination and degradation of ZIKV nonstructural protein 1 (NS1) and nonstructural protein 3 (NS3). Further studies showed that the SPRY domain and Ring domain of TRIM22 played important roles in protein interaction and degradation, respectively. In addition, we found that TRIM22 also inhibited other flaviviruses infection including dengue virus (DENV) and yellow fever virus (YFV). Conclusion Thus, TRIM22 is an ISG with important role in host defense against flaviviruses through binding and degradation of the NS1 and NS3 proteins.https://doi.org/10.1186/s13578-022-00872-wTRIM22Zika virusInfectionNonstructural proteinUbiquitination |
| spellingShingle | Shulong Zu Chunfeng Li Lili Li Yong-Qiang Deng Xiang Chen Dan Luo Qing Ye Yi-Jiao Huang Xiao-Feng Li Rong-Rong Zhang Nina Sun Xianqi Zhang Saba R. Aliyari Karin Nielsen-Saines Jae U. Jung Heng Yang Cheng-Feng Qin Genhong Cheng TRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradation Cell & Bioscience TRIM22 Zika virus Infection Nonstructural protein Ubiquitination |
| title | TRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradation |
| title_full | TRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradation |
| title_fullStr | TRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradation |
| title_full_unstemmed | TRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradation |
| title_short | TRIM22 suppresses Zika virus replication by targeting NS1 and NS3 for proteasomal degradation |
| title_sort | trim22 suppresses zika virus replication by targeting ns1 and ns3 for proteasomal degradation |
| topic | TRIM22 Zika virus Infection Nonstructural protein Ubiquitination |
| url | https://doi.org/10.1186/s13578-022-00872-w |
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