Evidence map›Paper›PMID 34281462›Full record

ArticleAutophagy2021

Manipulation of autophagy by SARS-CoV-2 proteins.

Lennart Koepke, Maximilian Hirschenberger, Manuel Hayn, Frank Kirchhoff, Konstantin Mj Sparrer

Open access · greenAbstract readComment
In one paragraph

Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
11.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
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  12. ELV-N34, RvD6-Isomer, or NPD1 Halt Replication of SARS-CoV-2 Omicron BA.5 Virus in Human Lung and Nasal Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Lennart KoepkeInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.ORCID 0000-0001-9788-1972
Maximilian HirschenbergerInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.ORCID 0000-0001-8766-1271
Manuel HaynInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.ORCID 0000-0001-5908-3099
Frank KirchhoffInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.ORCID 0000-0002-7052-2360
Konstantin Mj SparrerInstitute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.ORCID 0000-0002-8682-1779
Universität Ulm · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

COVID-19SARS-CoV-2AutophagosomesAutophagyHumansLysosomesAutophagyCOVID-19double-membrane vesiclesEnvelope proteininnate immunityMembrane proteinNsp15ORF3aORF7aSARS-CoVSARS-CoV-2

Identifiers

PMID34281462
PMCPMC8496524
OpenAlexW3183202855

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.