دورية أكاديمية

The recruitment of TRiC chaperonin in rotavirus viroplasms correlates with virus replication.

التفاصيل البيبلوغرافية
العنوان: The recruitment of TRiC chaperonin in rotavirus viroplasms correlates with virus replication.
المؤلفون: Vetter J; Institute of Virology, University of Zurich, Zurich, Switzerland., Papa G; Molecular Immunology Lab, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Tobler K; Institute of Virology, University of Zurich, Zurich, Switzerland., Rodriguez JM; Department of Structure of Macromolecules, Centro Nacional de Biotecnología/CSIC, Cantoblanco, Madrid, Spain., Kley M; Institute of Virology, University of Zurich, Zurich, Switzerland., Myers M; Proteomics Lab, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Wiesendanger M; Institute of Virology, University of Zurich, Zurich, Switzerland.; Institute of Veterinary Anatomy, University of Zurich, Zurich, Switzerland., Schraner EM; Institute of Virology, University of Zurich, Zurich, Switzerland.; Institute of Veterinary Anatomy, University of Zurich, Zurich, Switzerland., Luque D; School of Biomedical Sciences, The University of New South Wales, Sydney, New South Wales, Australia.; Electron Microscope Unit, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, New South Wales, Australia., Burrone OR; Molecular Immunology Lab, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Fraefel C; Institute of Virology, University of Zurich, Zurich, Switzerland., Eichwald C; Institute of Virology, University of Zurich, Zurich, Switzerland.
المصدر: MBio [mBio] 2024 Apr 10; Vol. 15 (4), pp. e0049924. Date of Electronic Publication: 2024 Mar 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Rotavirus*/genetics, Viral Replication Compartments/metabolism ; Viral Nonstructural Proteins/metabolism ; Cryoelectron Microscopy ; Virus Replication/physiology ; RNA ; Peptides
مستخلص: Rotavirus (RV) replication takes place in the viroplasms, cytosolic inclusions that allow the synthesis of virus genome segments and their encapsidation in the core shell, followed by the addition of the second layer of the virion. The viroplasms are composed of several viral proteins, including NSP5, which serves as the main building block. Microtubules, lipid droplets, and miRNA-7 are among the host components recruited in viroplasms. We investigated the interaction between RV proteins and host components of the viroplasms by performing a pull-down assay of lysates from RV-infected cells expressing NSP5-BiolD2. Subsequent tandem mass spectrometry identified all eight subunits of the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for folding at least 10% of the cytosolic proteins. Our confirmed findings reveal that TRiC is brought into viroplasms and wraps around newly formed double-layered particles. Chemical inhibition of TRiC and silencing of its subunits drastically reduced virus progeny production. Through direct RNA sequencing, we show that TRiC is critical for RV replication by controlling dsRNA genome segment synthesis, particularly negative-sense single-stranded RNA. Importantly, cryo-electron microscopy analysis shows that TRiC inhibition results in defective virus particles lacking genome segments and polymerase complex (VP1/VP3). Moreover, TRiC associates with VP2 and NSP5 but not with VP1. Also, VP2 is shown to be essential for recruiting TRiC in viroplasms and preserving their globular morphology. This study highlights the essential role of TRiC in viroplasm formation and in facilitating virion assembly during the RV life cycle.
Importance: The replication of rotavirus takes place in cytosolic inclusions termed viroplasms. In these inclusions, the distinct 11 double-stranded RNA genome segments are co-packaged to complete a genome in newly generated virus particles. In this study, we show for the first time that the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for the folding of at least 10% of the cytosolic proteins, is a component of viroplasms and is required for the synthesis of the viral negative-sense single-stranded RNA. Specifically, TRiC associates with NSP5 and VP2, the cofactor involved in RNA replication. Our study adds a new component to the current model of rotavirus replication, where TRiC is recruited to viroplasms to assist replication.
Competing Interests: The authors declare no conflict of interest.
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معلومات مُعتمدة: University of Zurich; predoctoral ICGEB fellowship
فهرسة مساهمة: Keywords: NSP5; TRiC; VP2; chaperones; double-stranded RNA virus; rotavirus; viral replication; viroplasm
المشرفين على المادة: 0 (Viral Nonstructural Proteins)
63231-63-0 (RNA)
0 (Peptides)
تواريخ الأحداث: Date Created: 20240312 Date Completed: 20240411 Latest Revision: 20240425
رمز التحديث: 20240425
مُعرف محوري في PubMed: PMC11005421
DOI: 10.1128/mbio.00499-24
PMID: 38470055
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.00499-24