IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27511-1.html
   My bibliography  Save this article

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

Author

Listed:
  • Keisuke Tabata

    (Heidelberg University
    Osaka University
    Osaka University)

  • Vibhu Prasad

    (Heidelberg University)

  • David Paul

    (Heidelberg University
    MRC Laboratory of Molecular Biology)

  • Ji-Young Lee

    (Heidelberg University)

  • Minh-Tu Pham

    (Heidelberg University)

  • Woan-Ing Twu

    (Heidelberg University)

  • Christopher J. Neufeldt

    (Heidelberg University)

  • Mirko Cortese

    (Heidelberg University)

  • Berati Cerikan

    (Heidelberg University)

  • Yannick Stahl

    (Heidelberg University)

  • Sebastian Joecks

    (Heidelberg University
    LI-COR Biosciences GmbH)

  • Cong Si Tran

    (Heidelberg University)

  • Christian Lüchtenborg

    (Heidelberg University)

  • Philip V’kovski

    (Institute of Virology and Immunology IVI
    University of Bern)

  • Katrin Hörmann

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • André C. Müller

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Carolin Zitzmann

    (University Medicine Greifswald
    Theoretical Biology and Biophysics)

  • Uta Haselmann

    (Heidelberg University)

  • Jürgen Beneke

    (Heidelberg University)

  • Lars Kaderali

    (University Medicine Greifswald)

  • Holger Erfle

    (Heidelberg University)

  • Volker Thiel

    (Institute of Virology and Immunology IVI
    University of Bern)

  • Volker Lohmann

    (Heidelberg University)

  • Giulio Superti-Furga

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Medical University of Vienna)

  • Britta Brügger

    (Heidelberg University)

  • Ralf Bartenschlager

    (Heidelberg University
    German Cancer Research Center
    Heidelberg Partner Site)

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.

Suggested Citation

  • Keisuke Tabata & Vibhu Prasad & David Paul & Ji-Young Lee & Minh-Tu Pham & Woan-Ing Twu & Christopher J. Neufeldt & Mirko Cortese & Berati Cerikan & Yannick Stahl & Sebastian Joecks & Cong Si Tran & C, 2021. "Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27511-1
    DOI: 10.1038/s41467-021-27511-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27511-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-27511-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Petter Holland & Helene Knævelsrud & Kristiane Søreng & Benan J. Mathai & Alf Håkon Lystad & Serhiy Pankiv & Gunnveig T. Bjørndal & Sebastian W. Schultz & Viola H. Lobert & Robin B. Chan & Bowen Zhou , 2016. "HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    2. Steffen Klein & Mirko Cortese & Sophie L. Winter & Moritz Wachsmuth-Melm & Christopher J. Neufeldt & Berati Cerikan & Megan L. Stanifer & Steeve Boulant & Ralf Bartenschlager & Petr Chlanda, 2020. "SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    3. Alessandro Pagliuso & Carmen Valente & Lucia Laura Giordano & Angela Filograna & Guiling Li & Diego Circolo & Gabriele Turacchio & Vincenzo Manuel Marzullo & Luigi Mandrich & Mikhail A. Zhukovsky & Fa, 2016. "Golgi membrane fission requires the CtBP1-S/BARS-induced activation of lysophosphatidic acid acyltransferase δ," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Liv Zimmermann & Xiaohan Zhao & Jana Makroczyova & Moritz Wachsmuth-Melm & Vibhu Prasad & Zach Hensel & Ralf Bartenschlager & Petr Chlanda, 2023. "SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Keisuke Tabata & Kenta Imai & Koki Fukuda & Kentaro Yamamoto & Hayato Kunugi & Toshiharu Fujita & Tatsuya Kaminishi & Christian Tischer & Beate Neumann & Sabine Reither & Fatima Verissimo & Rainer Pep, 2024. "Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Nell Saunders & Blandine Monel & Nadège Cayet & Lorenzo Archetti & Hugo Moreno & Alexandre Jeanne & Agathe Marguier & Julian Buchrieser & Timothy Wai & Olivier Schwartz & Mathieu Fréchin, 2024. "Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Katelyn C. Cook & Elene Tsopurashvili & Jason M. Needham & Sunnie R. Thompson & Ileana M. Cristea, 2022. "Restructured membrane contacts rewire organelles for human cytomegalovirus infection," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Paula P. Coelho & Geoffrey G. Hesketh & Annika Pedersen & Elena Kuzmin & Anne-Marie N. Fortier & Emily S. Bell & Colin D. H. Ratcliffe & Anne-Claude Gingras & Morag Park, 2022. "Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Andreia L. Pinto & Ranjit K. Rai & Jonathan C. Brown & Paul Griffin & James R. Edgar & Anand Shah & Aran Singanayagam & Claire Hogg & Wendy S. Barclay & Clare E. Futter & Thomas Burgoyne, 2022. "Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Francisco S. Mesquita & Laurence Abrami & Lucie Bracq & Nattawadee Panyain & Vincent Mercier & Béatrice Kunz & Audrey Chuat & Joana Carlevaro-Fita & Didier Trono & F. Gisou van der Goot, 2023. "SARS-CoV-2 hijacks a cell damage response, which induces transcription of a more efficient Spike S-acyltransferase," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Michael J. Munson & Benan J. Mathai & Matthew Yoke Wui Ng & Laura Trachsel-Moncho & Laura R. Ballina & Sebastian W. Schultz & Yahyah Aman & Alf H. Lystad & Sakshi Singh & Sachin Singh & Jørgen Wesche , 2021. "GAK and PRKCD are positive regulators of PRKN-independent mitophagy," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    6. Scotland E. Farley & Jennifer E. Kyle & Hans C. Leier & Lisa M. Bramer & Jules B. Weinstein & Timothy A. Bates & Joon-Yong Lee & Thomas O. Metz & Carsten Schultz & Fikadu G. Tafesse, 2022. "A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Leslie A. Rowland & Adilson Guilherme & Felipe Henriques & Chloe DiMarzio & Sean Munroe & Nicole Wetoska & Mark Kelly & Keith Reddig & Gregory Hendricks & Meixia Pan & Xianlin Han & Olga R. Ilkayeva &, 2023. "De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Emilie Murigneux & Laurent Softic & Corentin Aubé & Carmen Grandi & Delphine Judith & Johanna Bruce & Morgane Le Gall & François Guillonneau & Alain Schmitt & Vincent Parissi & Clarisse Berlioz-Torren, 2024. "Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Liv Zimmermann & Xiaohan Zhao & Jana Makroczyova & Moritz Wachsmuth-Melm & Vibhu Prasad & Zach Hensel & Ralf Bartenschlager & Petr Chlanda, 2023. "SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    10. Selma Dahmane & Adeline Kerviel & Dustin R. Morado & Kasturika Shankar & Björn Ahlman & Michael Lazarou & Nihal Altan-Bonnet & Lars-Anders Carlson, 2022. "Membrane-assisted assembly and selective secretory autophagy of enteroviruses," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. P. J. Schubert & R. Saxena & J. Kornfeld, 2024. "DeepFocus: fast focus and astigmatism correction for electron microscopy," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    12. Leonid Andronov & Mengting Han & Yanyu Zhu & Ashwin Balaji & Anish R. Roy & Andrew E. S. Barentine & Puja Patel & Jaishree Garhyan & Lei S. Qi & W. E. Moerner, 2024. "Nanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Morgane Mabire & Pushpa Hegde & Adel Hammoutene & Jinghong Wan & Charles Caër & Rola Al Sayegh & Mathilde Cadoux & Manon Allaire & Emmanuel Weiss & Tristan Thibault-Sogorb & Olivier Lantz & Michèle Go, 2023. "MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27511-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.