Evidence map›Paper›PMID 34788596›Full record

ArticleCell reports2021

Contribution of autophagy machinery factors to HCV and SARS-CoV-2 replication organelle formation.

Woan-Ing Twu, Ji-Young Lee, Heeyoung Kim, Vibhu Prasad, Berati Cerikan, Uta Haselmann, Keisuke Tabata, Ralf Bartenschlager

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
12.2field-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

71 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. From lipid overload to autophagy collapse: how lipid dysregulation drives chronic inflammation and metabolic disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
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  12. Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025
    Review
  13. Article
  14. Article
  15. Review
  16. 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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  20. Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Woan-Ing TwuDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
Ji-Young LeeDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
Heeyoung KimDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany; Center for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany.
Vibhu PrasadDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
Berati CerikanDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
Uta HaselmannDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany; Center for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany.
Keisuke TabataDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany; Center for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany; Division Virus-Associated Carcinogenesis, German Cancer Research Center, 69120 Heidelberg, Germany. Electronic address: ralf.bartenschlager@med.uni-heidelberg.de.
Heidelberg University · DEGerman Cancer Research Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Positive-strand RNA viruses replicate in close association with rearranged intracellular membranes. For hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these rearrangements comprise endoplasmic reticulum (ER)-derived double membrane vesicles (DMVs) serving as RNA replication sites. Cellular factors involved in DMV biogenesis are poorly defined. Here, we show that despite structural similarity of viral DMVs with autophagosomes, conventional macroautophagy is dispensable for HCV and SARS-CoV-2 replication. However, both viruses exploit factors involved in autophagosome formation, most notably class III phosphatidylinositol 3-kinase (PI3K). As revealed with a biosensor, PI3K is activated in cells infected with either virus to produce phosphatidylinositol 3-phosphate (PI3P) while kinase complex inhibition or depletion profoundly reduces replication and viral DMV formation. The PI3P-binding protein DFCP1, recruited to omegasomes in early steps of autophagosome formation, participates in replication and DMV formation of both viruses. These results indicate that phylogenetically unrelated HCV and SARS-CoV-2 exploit similar components of the autophagy machinery to create their replication organelles.

Indexed as

AutophagosomesAutophagyCarrier ProteinsClass III Phosphatidylinositol 3-KinasesHepacivirusHumansPhosphatidylinositol PhosphatesRNA, ViralSARS-CoV-2Viral Nonstructural ProteinsViral Replication CompartmentsVirus ReplicationCarrier ProteinsClass III Phosphatidylinositol 3-Kinasesphosphatidylinositol 3-phosphatePhosphatidylinositol PhosphatesRNA, ViralViral Nonstructural ProteinsZFYVE1 protein, humanautophagyBeclin 1class III PI3KcoronavirusdaclatasvirDFCP1DMVhepatitis C virusPI3Preplication organelle

Identifiers

PMID34788596
PMCPMC8577994
OpenAlexW3213294911

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.