Enhanced autophagosome formation

Stable Identifier
R-HSA-9698265
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
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This COVID‑19 event 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 replicase polyprotein 1a of the human severe acute respiratory syndrome coronavirus (SARS-CoV) is post-translationally cleaved by virally encoded proteases to generate non-structural proteins (nsps). Viral nsps induce the formation of ER-bound double membrane vesicles (DMV) in host cells post infection. These DMVs are decorated with microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) proteins that are involved in autophagosome formation. However, there is no evidence that DMVs are recruited to the autophagy machinery. Immunofluorescence studies show that nsp6 (Cottam E M. et al 2011) and nsp8 (Prentice E. et al 2004) colocalizes with MAP1LC3B suggesting a binding event. In some cell types, expression of sars9b (9b) triggers the formation of autophagosomes and underlying molecular mechanisms are unclear (Shi C S. et al 2014). Studies also show that sars8b (8b) can trigger cellular stress, which results in a calcineurin dependent Transcription Factor EB (TFEB) activation and its target genes. This leads to an increase in autophagic flux (Shi C S. et al 2019).

Literature References
PubMed ID Title Journal Year
25135833 SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome

Shi, CS, Qi, HY, Boularan, C, Huang, NN, Abu-Asab, M, Shelhamer, JH, Kehrl, JH

J. Immunol. 2014
21799305 Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate

Cottam, EM, Maier, HJ, Manifava, M, Vaux, LC, Chandra-Schoenfelder, P, Gerner, W, Britton, P, Ktistakis, NT, Wileman, T

Autophagy 2011
15331731 Identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins

Prentice, E, McAuliffe, J, Lu, X, Subbarao, K, Denison, MR

J. Virol. 2004
31231549 SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes

Shi, CS, Nabar, NR, Huang, NN, Kehrl, JH

Cell Death Discov 2019
Participants
Participates
This event is regulated
Inferred From
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
Reviewed
Created
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