Virion Assembly and Release

Stable Identifier
R-HSA-9694322
Type
Pathway
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
ReviewStatus
5/5
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Virion Assembly and Release
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This COVID-19 pathway has been created by a combination of computational inference from SARS-CoV-1 data (https://reactome.org/documentation/inferred-events) and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.

The structures of complete SARS-CoV-2 virions, as well as their assembly stages, have been elucidated in great detail by cryo-electron microscopy methods. In particular, the Spike trimer is localized to ERGIC or Golgi compartments upon coexpression of E or M, which prevents syncytia formation (Boson et al, 2020). It is then transported via small transport vesicles to assembly sites (Klein et al, 2020; Mendonça et al, 2021; reviewed by Hardenbrook and Zhang, 2021). Based on work done in related coronaviruses, viral assembly is expected to occur at the ERGIC membrane (reviewed in Masters, 2006; Fehr and Perlman, 2015; Fung and Liu, 2019). Membrane protein components of the virus concentrate at the ERGIC membrane but are also found throughout the secretory system including at the plasma membrane. Accumulation at the site of viral assembly has been shown to depend on interaction between retrieval signals in the cytoplasmic tails of viral proteins and host factors such as the COPI coat, and likely involves repeated rounds of anterograde and retrograde traffic (McBride et al, 2007; Ujike et al, 2016; Tan et al, 2004; Tan et al, 2005; reviewed in McBride and Fielding, 2012; Chang et al, 2014).
Viral assembly is initiated by homotypic interactions of M protein (Tseng et al, 2010; Siu et al, 2008). This forms an M-lattice that contributes to the induction of membrane curvature and additionally acts as a scaffold for the recruitment of the other structural components of the virus (Voss et al, 2009). M protein makes interactions with each of the main components of the mature virus, including E, S and N (He et al, 2004; Luo et al, 2006; Siu et al, 2008; reviewed in Masters, 2006). Electron micrographic studies suggest the final size of the mature virus is ~100 nm. The ribonuclear particle is predominantly helical and is packaged with an outer diamter of ~ 16 nm (Neuman et al, 2006; Neuman et al, 2011; reviewed in Chang et al, 2014). These physical constraints suggest a final stoichiometry in the mature virion of 75 S trimers:1200 M proteins:300 N:1 RNA genome (Neuman et al, 2011; reviewed in Chang et al, 2014). Minor amounts of other viral proteins, including proteins E, 3a and 7a may also be components of the mature virus, although their functions are not well established (reviewed in Schoeman and Fielding, 2019; Liu et al, 2014).
Literature References
PubMed ID Title Journal Year
33229438 The SARS-CoV-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles

Denolly, S, Lavillette, D, Siret, E, Boson, B, Zhou, B, Mathieu, C, Cosset, FL, Legros, V

J Biol Chem 2021
34330917 Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress

Sun, D, Mendonça, L, Radecke, J, Martin-Fernandez, ML, Krebs, AS, Howe, A, Chen, L, Li, VD, Kounatidis, I, Sheng, Y, Gilchrist, JB, Bateman, B, Zhang, P, James, W, Harkiolaki, M, Koronfel, MA, Ni, T, Zanetti-Domingues, LC, Szynkiewicz, M, Knight, ML

Nat Commun 2021
20154085 Self-assembly of severe acute respiratory syndrome coronavirus membrane protein

Tseng, YT, Wang, SM, Chiang, CC, Huang, KJ, Lee, AI, Wang, CT

J. Biol. Chem. 2010
34915287 A structural view of the SARS-CoV-2 virus and its assembly

Zhang, P, Hardenbrook, NJ

Curr Opin Virol 2021
33208793 SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography

Chlanda, P, Wachsmuth-Melm, M, Winter, SL, Cerikan, B, Bartenschlager, R, Stanifer, ML, Boulant, S, Klein, S, Neufeldt, CJ, Cortese, M

Nat Commun 2020
31133031 Coronavirus envelope protein: current knowledge

Schoeman, D, Fielding, BC

Virol. J. 2019
16873249 Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy

Neuman, BW, Buchmeier, MJ, Milligan, RA, Yeager, M, Adair, BD, Orca, G, Kuhn, P, Yoshioka, C, Quispe, JD

J. Virol. 2006
15351485 Characterization of protein-protein interactions between the nucleocapsid protein and membrane protein of the SARS coronavirus

Li, Y, Tyler, S, Strocher, U, Booth, TF, Theriault, S, Bastien, N, Baker, L, He, R, Plummer, FA, Cao, J, Feldmann, H, Cutts, T, Ballantine, M, Li, X, Dobie, F, Leeson, A, Andonov, A

Virus Res. 2004
25720466 Coronaviruses: an overview of their replication and pathogenesis

Perlman, S, Fehr, AR

Methods Mol. Biol. 2015
23202509 The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis

McBride, R, Fielding, BC

Viruses 2012
17166901 The cytoplasmic tail of the severe acute respiratory syndrome coronavirus spike protein contains a novel endoplasmic reticulum retrieval signal that binds COPI and promotes interaction with membrane protein

Li, J, Machamer, CE, McBride, CE

J. Virol. 2007
16343974 Severe acute respiratory syndrome coronavirus membrane protein interacts with nucleocapsid protein mostly through their carboxyl termini by electrostatic attraction

Shen, X, Shen, C, Luo, H, Jiang, H, Wu, D, Chen, K

Int. J. Biochem. Cell Biol. 2006
18753196 The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles

Nicholls, JM, Nal, B, Altmeyer, R, Bruzzone, R, Teoh, KT, Kien, F, Chan, CM, Escriou, N, Tsao, SW, Peiris, JS, Siu, YL, Lo, J

J. Virol. 2008
15194747 A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis

Tan, TH, Hong, W, Teng, E, Tan, YJ, Fielding, BC, Ooi, EE, Lim, SG, Tan, HC, Shen, S, Goh, PY

J. Virol. 2004
27145752 The contribution of the cytoplasmic retrieval signal of severe acute respiratory syndrome coronavirus to intracellular accumulation of S proteins and incorporation of S protein into virus-like particles

Ujike, M, Huang, C, Makino, S, Shirato, K, Taguchi, F

J. Gen. Virol. 2016
15703085 The Severe Acute Respiratory Syndrome (SARS)-coronavirus 3a protein may function as a modulator of the trafficking properties of the spike protein

Tan, YJ

Virol. J. 2005
19534833 Studies on membrane topology, N-glycosylation and functionality of SARS-CoV membrane protein

Voss, D, Drosten, C, Lanzavecchia, A, Pfefferle, S, Stevermann, L, Becker, S, Traggiai, E

Virol. J. 2009
16877062 The molecular biology of coronaviruses

Masters, PS

Adv. Virus Res. 2006
24418573 The SARS coronavirus nucleocapsid protein--forms and functions

Chang, CK, Hsiao, CD, Hou, MH, Chang, CF, Huang, TH

Antiviral Res. 2014
31226023 Human Coronavirus: Host-Pathogen Interaction

Fung, TS, Liu, DX

Annu. Rev. Microbiol. 2019
24995382 Accessory proteins of SARS-CoV and other coronaviruses

Hilgenfeld, R, Fung, TS, Liu, DX, Shukla, A, Chong, KK

Antiviral Res. 2014
Participants
Events
Participates
as an event of
Inferred From
Virion Assembly and Release (Homo sapiens)
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Rothfels, K  (2020-07-30)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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