Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist
Abstract Background Rhinoviruses (RVs) cause more than half of common colds and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host factors, few of which have proven clinical relevance. Results Herein, we...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Genome Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13059-021-02513-w |
| _version_ | 1819037905497096192 |
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| author | Hong Mei Zhao Zha Wei Wang Yusang Xie Yuege Huang Wenping Li Dong Wei Xinxin Zhang Jieming Qu Jia Liu |
| author_facet | Hong Mei Zhao Zha Wei Wang Yusang Xie Yuege Huang Wenping Li Dong Wei Xinxin Zhang Jieming Qu Jia Liu |
| author_sort | Hong Mei |
| collection | DOAJ |
| description | Abstract Background Rhinoviruses (RVs) cause more than half of common colds and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host factors, few of which have proven clinical relevance. Results Herein, we systematically compare genome-wide CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome CRISPR screen, for their efficiencies in identifying RV host factors. We find that surfaceome screen outperforms the genome-wide screen in the success rate of hit identification. Importantly, using the surfaceome screen, we identify olfactomedin-like 3 (OLFML3) as a novel host factor of RV serotypes A and B, including a clinical isolate. We find that OLFML3 is a RV-inducible suppressor of the innate immune response and that OLFML3 antagonizes type I interferon (IFN) signaling in a SOCS3-dependent manner. Conclusion Our study suggests that RV-induced OLFML3 expression is an important mechanism for RV to hijack the immune system and underscores surfaceome CRISPR screen in identifying viral host factors. |
| first_indexed | 2024-12-21T08:28:51Z |
| format | Article |
| id | doaj.art-9f7d98422fb34b7e88ced119dbb2f4ce |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-21T08:28:51Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-9f7d98422fb34b7e88ced119dbb2f4ce2022-12-21T19:10:16ZengBMCGenome Biology1474-760X2021-10-0122112410.1186/s13059-021-02513-wSurfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonistHong Mei0Zhao Zha1Wei Wang2Yusang Xie3Yuege Huang4Wenping Li5Dong Wei6Xinxin Zhang7Jieming Qu8Jia Liu9Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityDepartment of Respiratory and Critical Care Medicine, Ruijin Hospital and Institutes of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityResearch Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineResearch Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Respiratory and Critical Care Medicine, Ruijin Hospital and Institutes of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityAbstract Background Rhinoviruses (RVs) cause more than half of common colds and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host factors, few of which have proven clinical relevance. Results Herein, we systematically compare genome-wide CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome CRISPR screen, for their efficiencies in identifying RV host factors. We find that surfaceome screen outperforms the genome-wide screen in the success rate of hit identification. Importantly, using the surfaceome screen, we identify olfactomedin-like 3 (OLFML3) as a novel host factor of RV serotypes A and B, including a clinical isolate. We find that OLFML3 is a RV-inducible suppressor of the innate immune response and that OLFML3 antagonizes type I interferon (IFN) signaling in a SOCS3-dependent manner. Conclusion Our study suggests that RV-induced OLFML3 expression is an important mechanism for RV to hijack the immune system and underscores surfaceome CRISPR screen in identifying viral host factors.https://doi.org/10.1186/s13059-021-02513-wCRISPRGenome-wide screenSurfaceome screenRhinovirusOLFML3 |
| spellingShingle | Hong Mei Zhao Zha Wei Wang Yusang Xie Yuege Huang Wenping Li Dong Wei Xinxin Zhang Jieming Qu Jia Liu Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist Genome Biology CRISPR Genome-wide screen Surfaceome screen Rhinovirus OLFML3 |
| title | Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist |
| title_full | Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist |
| title_fullStr | Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist |
| title_full_unstemmed | Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist |
| title_short | Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist |
| title_sort | surfaceome crispr screen identifies olfml3 as a rhinovirus inducible ifn antagonist |
| topic | CRISPR Genome-wide screen Surfaceome screen Rhinovirus OLFML3 |
| url | https://doi.org/10.1186/s13059-021-02513-w |
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