Evidence map›Paper›PMID 34907161›Full record

ArticleNature communications2021

Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation.

Keisuke Tabata, Vibhu Prasad, David Paul, Ji-Young Lee, Minh-Tu Pham, Woan-Ing Twu, Christopher J Neufeldt, Mirko Cortese, Berati Cerikan, Yannick Stahl and 16 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 79 citations in OpenAlex.

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  15. Structural insights into SARS-CoV-2 nonstructural protein 4 (nsp4) biogenesis.Protein science : a publication of the Protein Society · 2025
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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

26 authors at 8 institutions in 6 countries.

Keisuke Tabata *Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-6776-1689
Vibhu Prasad *Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-7450-607X
David PaulDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-6652-331X
Ji-Young LeeDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Minh-Tu PhamDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Woan-Ing TwuDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Christopher J NeufeldtDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-4551-1811
Mirko CorteseDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-1786-4211
Berati CerikanDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Yannick StahlDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0861-4907
Sebastian JoecksDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Cong Si TranDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Christian LüchtenborgBiochemistry Center Heidelberg, Heidelberg University, Heidelberg, Germany.
Philip V'kovskiInstitute of Virology and Immunology IVI, Bern, Switzerland.ORCID http://orcid.org/0000-0002-8366-1220
Katrin HörmannCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
André C MüllerCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Carolin ZitzmannInstitute of Bioinformatics and Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany.
Uta HaselmannDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
Jürgen BenekeBioQuant, Heidelberg University, Heidelberg, Germany.
Lars KaderaliInstitute of Bioinformatics and Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-2359-2294
Holger ErfleBioQuant, Heidelberg University, Heidelberg, Germany.
Volker ThielInstitute of Virology and Immunology IVI, Bern, Switzerland.ORCID http://orcid.org/0000-0002-5783-0887
Volker LohmannDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8719-7608
Giulio Superti-FurgaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID http://orcid.org/0000-0002-0570-1768
Britta BrüggerBiochemistry Center Heidelberg, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-3477-8270
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany. ralf.bartenschlager@med.uni-heidelberg.de.ORCID http://orcid.org/0000-0001-5601-9307
Heidelberg University · DEAustrian Academy of Sciences · ATGerman Cancer Research Center · DELos Alamos National Laboratory · USMRC Laboratory of Molecular Biology · GBSiemens (Germany) · DEUniversitätsmedizin Greifswald · DEUniversity of Bern · CH

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) grant number 031A602A (ERASysApp SysVirDrug)Deutsche Forschungsgemeinschaft (German Research Foundation) Project Number 112927078 - TRR 83Deutsche Forschungsgemeinschaft (German Research Foundation) Project Number 272983813 - TRR 179Deutsche Forschungsgemeinschaft (German Research Foundation) Project Number 314905040 - TRR 209European Molecular Biology Organization (EMBO) ALTF 454-2020European Molecular Biology Organization (EMBO) ALTF 466-2016Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) Swiss National Science foundation (SNF Project Number 310030_173085
6 · The paper itself

Abstract

Double membrane vesicles (DMVs) serve as replication organelles of plus-strand RNA viruses such as hepatitis C virus (HCV) and SARS-CoV-2. Viral DMVs are morphologically analogous to DMVs formed during autophagy, but lipids driving their biogenesis are largely unknown. Here we show that production of the lipid phosphatidic acid (PA) by acylglycerolphosphate acyltransferase (AGPAT) 1 and 2 in the ER is important for DMV biogenesis in viral replication and autophagy. Using DMVs in HCV-replicating cells as model, we found that AGPATs are recruited to and critically contribute to HCV and SARS-CoV-2 replication and proper DMV formation. An intracellular PA sensor accumulated at viral DMV formation sites, consistent with elevated levels of PA in fractions of purified DMVs analyzed by lipidomics. Apart from AGPATs, PA is generated by alternative pathways and their pharmacological inhibition also impaired HCV and SARS-CoV-2 replication as well as formation of autophagosome-like DMVs. These data identify PA as host cell lipid involved in proper replication organelle formation by HCV and SARS-CoV-2, two phylogenetically disparate viruses causing very different diseases, i.e. chronic liver disease and COVID-19, respectively. Host-targeting therapy aiming at PA synthesis pathways might be suitable to attenuate replication of these viruses.

Indexed as

1-Acylglycerol-3-Phosphate O-AcyltransferaseAcyltransferasesAutophagosomesAutophagyCell LineCell SurvivalCOVID-19Dengue VirusHEK293 CellsHepacivirusHumansMembrane ProteinsPhosphatidic AcidsSARS-CoV-2Spike Glycoprotein, CoronavirusViral Nonstructural Proteins1-Acylglycerol-3-Phosphate O-Acyltransferase2-acylglycerophosphate acyltransferaseAcyltransferasesAGPAT1 protein, humanMembrane ProteinsNS4B protein, Dengue virusPhosphatidic AcidsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Viral Nonstructural ProteinsViral Proteins

Identifiers

PMID34907161
PMCPMC8671429
OpenAlexW4225357678

What OpenQuestion holds

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LicenceCC BY
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.