SARS-CoV-2 modulates autophagy

Stable Identifier
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
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Autophagy is activated during microbial infection to exert antimicrobial defense mechanisms by targeting pathogen-associated components for lysosomal degradation. Pathogens evolved various strategies to manipulate autophagy responses. This Reactome module describes the impact of SARS-CoV-2 infection on autophagy. SARS-CoV-2-encoded proteins, such as open reading frame 3a (ORF3a, 3a) and ORF7a (7a), were shown to colocalize with markers of late endosomal membrane, lysosomal membrane and trans-Golgi network (Hayn M et al. 2021; Koepke L et al. 2021; Zhang Y et al. 2021). Both 3a and 7a block autophagic flux in human cells, but use different strategies (Hayn M et al. 2021; Koepke L et al. 2021). While 7a lowers the acidity of lysosome (Koepke L et al. 2021), ORF3a prevents autophagosome-lysosome fusion (Zhang Y et al. 2021; Qu Y et al. 2021; Miao G et al. 2021). Thus, the SARS-CoV-2 infection stimulates autophagy and leads to an accumulation of autophagosomes but blocks fusion between autophagosome and lysosome thereby preventing degradation of the cargo. In addition, SARS-CoV-2 membrane (M) protein associates with the mitochondrion to promote mitophagy (Hui X et al. 2021).
Literature References
PubMed ID Title Journal Year
34440791 The Molecular Interplay between Human Coronaviruses and Autophagy

Nazarko, TY, Shroff, A

Cells 2021
33974846 Systematic functional analysis of SARS-CoV-2 proteins uncovers viral innate immune antagonists and remaining vulnerabilities

Stürzel, CM, Conzelmann, KK, Hunszinger, V, Müller, JA, Münch, J, Christensen, MH, Prelli Bozzo, C, Zech, F, Sparrer, KMJ, Hayn, M, Stenger, S, Aftab, W, Straub, JH, Kirchhoff, F, Hirschenberger, M, Srinivasachar Badarinarayan, S, Klute, S, Nchioua, R, Conzelmann, C, Forne, I, Imhof, A, Sauter, D, Koepke, L, Schmidt, FI

Cell Rep 2021
34386498 ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication

Liang, Q, Liu, C, Hu, G, Qu, Y, Zhang, Y, Li, J, Wang, W, Ren, S, Li, P, Wang, C, Liu, Z, Zhu, Y, Fu, J, Wang, Y, Wang, X, Zhang, R, Xiao, MZX

Front Cell Dev Biol 2021
33966045 SARS-CoV-2 promote autophagy to suppress type I interferon response

Jin, M, Cao, L, Chen, M, Chen, X, Zhang, Y, Lin, X, Zhao, Y, Hui, X, Huang, K, Zhang, L

Signal Transduct Target Ther 2021
33947832 The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes

Zhang, Y, Pei, R, Lin, Y, Mao, B, Sun, H, Lu, K, Zhao, Z, Li, H

Cell Discov 2021
34281462 Manipulation of autophagy by SARS-CoV-2 proteins

Kirchhoff, F, Hirschenberger, M, Hayn, M, Koepke, L, Sparrer, KM

Autophagy 2021
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
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