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Manipulation of autophagy by SARS-CoV-2 proteins.
Koepke, Lennart; Hirschenberger, Maximilian; Hayn, Manuel; Kirchhoff, Frank; Sparrer, Konstantin Mj.
  • Koepke L; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Hirschenberger M; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Hayn M; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Kirchhoff F; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Sparrer KM; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
Autophagy ; 17(9): 2659-2661, 2021 09.
Article in English | MEDLINE | ID: covidwho-1317864
ABSTRACT
As part of innate immune defenses, macroautophagy/autophagy targets viruses and viral components for lysosomal degradation and exposes pathogen-associated molecular patterns to facilitate recognition. However, viruses evolved sophisticated strategies to antagonize autophagy and even exploit it to promote their replication. In our recent study, we systematically analyzed the impact of individual SARS-CoV-2 proteins on autophagy. We showed that E, M, ORF3a, and ORF7a cause an accumulation of autophagosomes, whereas Nsp15 prevents the efficient formation of autophagosomes. Consequently, autophagic degradation of SQSTM1/p62 is decreased in the presence of E, ORF3a, ORF7a, and Nsp15. Notably, M does not alter SQSTM1 protein levels and colocalizes with accumulations of LC3B-positive membranes not resembling vesicles. Infection with SARS-CoV-2 prevents SQSTM1 degradation and increases lipidation of LC3B, indicating overall that the infection causes a reduction of autophagic flux. Our mechanistic analyses showed that the accessory proteins ORF3a and ORF7a both block autophagic degradation but use different strategies. While ORF3a prevents the fusion between autophagosomes and lysosomes, ORF7a reduces the acidity of lysosomes. In summary, we found that Nsp15, E, M, ORF3a, and ORF7a of SARS-CoV-2 manipulate cellular autophagy, and we determined the molecular mechanisms of ORF3a and ORF7a.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Autophagy Year: 2021 Document Type: Article Affiliation country: 15548627.2021.1953847

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Autophagy Year: 2021 Document Type: Article Affiliation country: 15548627.2021.1953847