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The SARS-CoV-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles.
J Biol Chem. 2021 Jan-Jun; 296:100111.JB

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a β-coronavirus, is the causative agent of the COVID-19 pandemic. Like for other coronaviruses, its particles are composed of four structural proteins: spike (S), envelope (E), membrane (M), and nucleoprotein (N) proteins. The involvement of each of these proteins and their interactions are critical for assembly and production of β-coronavirus particles. Here, we sought to characterize the interplay of SARS-CoV-2 structural proteins during the viral assembly process. By combining biochemical and imaging assays in infected versus transfected cells, we show that E and M regulate intracellular trafficking of S as well as its intracellular processing. Indeed, the imaging data reveal that S is relocalized at endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) or Golgi compartments upon coexpression of E or M, as observed in SARS-CoV-2-infected cells, which prevents syncytia formation. We show that a C-terminal retrieval motif in the cytoplasmic tail of S is required for its M-mediated retention in the ERGIC, whereas E induces S retention by modulating the cell secretory pathway. We also highlight that E and M induce a specific maturation of N-glycosylation of S, independently of the regulation of its localization, with a profile that is observed both in infected cells and in purified viral particles. Finally, we show that E, M, and N are required for optimal production of virus-like-particles. Altogether, these results highlight how E and M proteins may influence the properties of S proteins and promote the assembly of SARS-CoV-2 viral particles.

Authors+Show Affiliations

CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France.CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France; Université de Lyon, VetAgro Sup, Marcy-l'Étoile, France.Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France.CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France.CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France.CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai Chinese Academy of Sciences, Pasteurien College, Soochow University, Jiangsu, China.CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France. Electronic address: solene.denolly@ens-lyon.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33229438

Citation

Boson, Bertrand, et al. "The SARS-CoV-2 Envelope and Membrane Proteins Modulate Maturation and Retention of the Spike Protein, Allowing Assembly of Virus-like Particles." The Journal of Biological Chemistry, vol. 296, 2021, p. 100111.
Boson B, Legros V, Zhou B, et al. The SARS-CoV-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles. J Biol Chem. 2021;296:100111.
Boson, B., Legros, V., Zhou, B., Siret, E., Mathieu, C., Cosset, F. L., Lavillette, D., & Denolly, S. (2021). The SARS-CoV-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles. The Journal of Biological Chemistry, 296, 100111. https://doi.org/10.1074/jbc.RA120.016175
Boson B, et al. The SARS-CoV-2 Envelope and Membrane Proteins Modulate Maturation and Retention of the Spike Protein, Allowing Assembly of Virus-like Particles. J Biol Chem. 2021 Jan-Jun;296:100111. PubMed PMID: 33229438.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The SARS-CoV-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles. AU - Boson,Bertrand, AU - Legros,Vincent, AU - Zhou,Bingjie, AU - Siret,Eglantine, AU - Mathieu,Cyrille, AU - Cosset,François-Loïc, AU - Lavillette,Dimitri, AU - Denolly,Solène, Y1 - 2020/12/03/ PY - 2020/09/25/received PY - 2020/11/13/revised PY - 2020/11/23/accepted PY - 2020/11/25/pubmed PY - 2021/7/14/medline PY - 2020/11/24/entrez KW - COVID-19 KW - SARS-CoV KW - glycoprotein KW - infectious disease KW - secretion KW - viral protein KW - virus assembly SP - 100111 EP - 100111 JF - The Journal of biological chemistry JO - J Biol Chem VL - 296 N2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a β-coronavirus, is the causative agent of the COVID-19 pandemic. Like for other coronaviruses, its particles are composed of four structural proteins: spike (S), envelope (E), membrane (M), and nucleoprotein (N) proteins. The involvement of each of these proteins and their interactions are critical for assembly and production of β-coronavirus particles. Here, we sought to characterize the interplay of SARS-CoV-2 structural proteins during the viral assembly process. By combining biochemical and imaging assays in infected versus transfected cells, we show that E and M regulate intracellular trafficking of S as well as its intracellular processing. Indeed, the imaging data reveal that S is relocalized at endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) or Golgi compartments upon coexpression of E or M, as observed in SARS-CoV-2-infected cells, which prevents syncytia formation. We show that a C-terminal retrieval motif in the cytoplasmic tail of S is required for its M-mediated retention in the ERGIC, whereas E induces S retention by modulating the cell secretory pathway. We also highlight that E and M induce a specific maturation of N-glycosylation of S, independently of the regulation of its localization, with a profile that is observed both in infected cells and in purified viral particles. Finally, we show that E, M, and N are required for optimal production of virus-like-particles. Altogether, these results highlight how E and M proteins may influence the properties of S proteins and promote the assembly of SARS-CoV-2 viral particles. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/33229438/The_SARS_CoV_2_envelope_and_membrane_proteins_modulate_maturation_and_retention_of_the_spike_protein_allowing_assembly_of_virus_like_particles_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)00101-5 DB - PRIME DP - Unbound Medicine ER -