دورية أكاديمية
Liquid-liquid phase separation is essential for reovirus viroplasm formation and immune evasion.
| العنوان: | Liquid-liquid phase separation is essential for reovirus viroplasm formation and immune evasion. |
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| المؤلفون: | He L; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.; University of Chinese Academy of Sciences, Beijing, China., Wang Q; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.; University of Chinese Academy of Sciences, Beijing, China., Wang X; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.; University of Chinese Academy of Sciences, Beijing, China., Zhou F; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China., Yang C; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China., Li Y; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China., Liao L; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China., Zhu Z; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China., Ke F; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.; University of Chinese Academy of Sciences, Beijing, China., Wang Y; State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.; Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China. |
| المصدر: | Journal of virology [J Virol] 2024 Sep 17; Vol. 98 (9), pp. e0102824. Date of Electronic Publication: 2024 Aug 28. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Immune Evasion* , Reoviridae*/genetics , Reoviridae*/physiology , Virus Replication* , Viral Nonstructural Proteins*/metabolism , Viral Nonstructural Proteins*/genetics , Carps*/virology , Reoviridae Infections*/virology, Animals ; Inclusion Bodies, Viral/metabolism ; Fish Diseases/virology ; Fish Diseases/immunology ; Cytoplasm/virology ; Cytoplasm/metabolism ; Genome, Viral ; Cell Line ; RNA, Viral/genetics ; Phase Separation |
| مستخلص: | Grass carp reovirus (GCRV) is the most virulent pathogen in the genus Aquareovirus , belonging to the family Spinareoviridae . Members of the Spinareoviridae family are known to replicate and assemble in cytoplasmic inclusion bodies termed viroplasms; however, the detailed mechanism underlying GCRV viroplasm formation and its specific roles in virus infection remains largely unknown. Here, we demonstrate that GCRV viroplasms form through liquid-liquid phase separation (LLPS) of the nonstructural protein NS80 and elucidate the specific role of LLPS during reovirus infection and immune evasion. We observe that viroplasms coalesce within the cytoplasm of GCRV-infected cells. Immunofluorescence and transmission electron microscopy indicate that GCRV viroplasms are membraneless structures. Live-cell imaging and fluorescence recovery after photobleaching assay reveal that GCRV viroplasms exhibit liquid-like properties and are highly dynamic structures undergoing fusion and fission. Furthermore, by using a reagent to inhibit the LLPS process and constructing an NS80 mutant defective in LLPS, we confirm that the liquid-like properties of viroplasms are essential for recruiting viral dsRNA, viral RdRp, and viral proteins to participate in viral genome replication and virion assembly, as well as for sequestering host antiviral factors for immune evasion. Collectively, our findings provide detailed insights into reovirus viroplasm formation and reveal the specific functions of LLPS during virus infection and immune evasion, identifying potential targets for the prevention and control of this virus. Importance: Grass carp reovirus (GCRV) poses a significant threat to the aquaculture industry, particularly in China, where grass carp is a vital commercial fish species. However, detailed information regarding how GCRV viroplasms form and their specific roles in GCRV infection remains largely unknown. We discovered that GCRV viroplasms exhibit liquid-like properties and are formed through a physico-chemical biological phenomenon known as liquid-liquid phase separation (LLPS), primarily driven by the nonstructural protein NS80. Furthermore, we confirmed that the liquid-like properties of viroplasms are essential for virus replication, assembly, and immune evasion. Our study not only contributes to a deeper understanding of GCRV infection but also sheds light on broader aspects of viroplasm biology. Given that viroplasms are a universal feature of reovirus infection, inhibiting LLPS and then blocking viroplasms formation may serve as a potential pan-reovirus inhibition strategy. Competing Interests: The authors declare no conflict of interest. |
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| معلومات مُعتمدة: | XDB0730100 Strategic Priority Research Program of the Chinese Academy of Sciences; 32073017 MOST | National Natural Science Foundation of China (NSFC); U20A2063 MOST | National Natural Science Foundation of China (NSFC); 2021338 Youth Innovation Promotion Association of the Chinese Academy of Sciences (CAS YIPA) |
| فهرسة مساهمة: | Keywords: grass carp reovirus; immune evasion; liquid-liquid phase separation; nonstructural protein NS80; viroplasms; virus replication and assembly |
| المشرفين على المادة: | 0 (Viral Nonstructural Proteins) 0 (RNA, Viral) |
| تواريخ الأحداث: | Date Created: 20240828 Date Completed: 20240917 Latest Revision: 20240919 |
| رمز التحديث: | 20240919 |
| مُعرف محوري في PubMed: | PMC11406895 |
| DOI: | 10.1128/jvi.01028-24 |
| PMID: | 39194247 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
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| DOI: | 10.1128/jvi.01028-24 |