Nsp3, nsp4, and nsp6 produce replicative organelles

Stable Identifier
R-HSA-9694317
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
endoplasmic reticulum membrane, double membrane vesicle viral factory outer membrane
ReviewStatus
5/5
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Nsp3, nsp4, and nsp6 produce replicative organelles
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This COVID-19 event has been created by a combination of computational inference (see https://reactome.org/documentation/inferred-events) from SARS-CoV-1 data and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.

nsp3 and nsp4 alone caused considerable ER membrane deformation, producing a perinuclear double-walled maze-like body (MLB), and the nsp3–nsp4 interaction was shown to be absolutely necessary for such membrane rearrangement. Further necessary factors are nsp6 and unidentified host factors (Angelini et al 2013, Sakai et al 2017). nsp6 by itself can form Atg5 and LC3II-positive vesicles classically observed in autophagy (Cottam et al, 2014). However, in mouse hepatitis virus (MHV) infections, EDEM1 and OS9 of the ER-associated degradation system have been shown to be necessary co-factors (Reggiori et al, 2010)
Literature References
PubMed ID Title Journal Year
23943763 Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles

Angelini, MM, Akhlaghpour, M, Neuman, BW, Buchmeier, MJ

mBio 2013
28738245 Two-amino acids change in the nsp4 of SARS coronavirus abolishes viral replication

Sakai, Y, Kawachi, K, Terada, Y, Omori, H, Matsuura, Y, Kamitani, W

Virology 2017
24991833 Coronavirus NSP6 restricts autophagosome expansion

Cottam, EM, Whelband, MC, Wileman, T

Autophagy 2014
20542253 Coronaviruses Hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication

Reggiori, F, Monastyrska, I, Verheije, MH, Calì, T, Ulasli, M, Bianchi, S, Bernasconi, R, de Haan, CA, Molinari, M

Cell Host Microbe 2010
Participants
Input
Output
Participates
as an event of
Inferred From
Nsp3, nsp4, and nsp6 produce replicative organelles (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
Cross References
Mondo
Authored
Stephan, R  (2020-08-28)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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