IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30134-9.html
   My bibliography  Save this article

Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen

Author

Listed:
  • Alice Mac Kain

    (Université de Paris Cité)

  • Ghizlane Maarifi

    (, Université de Montpellier, CNRS)

  • Sophie-Marie Aicher

    (Université de Paris Cité)

  • Nathalie Arhel

    (, Université de Montpellier, CNRS)

  • Artem Baidaliuk

    (Institut Pasteur, G5 Evolutionary genomics of RNA viruses)

  • Sandie Munier

    (Université de Paris Cité
    CNR Virus des infections respiratoires)

  • Flora Donati

    (Université de Paris Cité
    CNR Virus des infections respiratoires)

  • Thomas Vallet

    (Université de Paris Cité)

  • Quang Dinh Tran

    (Université de Paris Cité)

  • Alexandra Hardy

    (Université de Paris Cité)

  • Maxime Chazal

    (Université de Paris Cité)

  • Françoise Porrot

    (Université de Paris Cité)

  • Molly OhAinle

    (Fred Hutchinson Cancer Research Center)

  • Jared Carlson-Stevermer

    (Synthego Corporation)

  • Jennifer Oki

    (Synthego Corporation)

  • Kevin Holden

    (Synthego Corporation)

  • Gert Zimmer

    (University of Bern)

  • Etienne Simon-Lorière

    (Institut Pasteur, G5 Evolutionary genomics of RNA viruses)

  • Timothée Bruel

    (Université de Paris Cité)

  • Olivier Schwartz

    (Université de Paris Cité)

  • Sylvie van der Werf

    (Université de Paris Cité
    CNR Virus des infections respiratoires)

  • Nolwenn Jouvenet

    (Université de Paris Cité)

  • Sébastien Nisole

    (, Université de Montpellier, CNRS)

  • Marco Vignuzzi

    (Université de Paris Cité)

  • Ferdinand Roesch

    (Université de Paris Cité
    UMR 1282 ISP, INRAE Centre Val de Loire)

Abstract

Interferon restricts SARS-CoV-2 replication in cell culture, but only a handful of Interferon Stimulated Genes with antiviral activity against SARS-CoV-2 have been identified. Here, we describe a functional CRISPR/Cas9 screen aiming at identifying SARS-CoV-2 restriction factors. We identify DAXX, a scaffold protein residing in PML nuclear bodies known to limit the replication of DNA viruses and retroviruses, as a potent inhibitor of SARS-CoV-2 and SARS-CoV replication in human cells. Basal expression of DAXX is sufficient to limit the replication of SARS-CoV-2, and DAXX over-expression further restricts infection. DAXX restricts an early, post-entry step of the SARS-CoV-2 life cycle. DAXX-mediated restriction of SARS-CoV-2 is independent of the SUMOylation pathway but dependent on its D/E domain, also necessary for its protein-folding activity. SARS-CoV-2 infection triggers the re-localization of DAXX to cytoplasmic sites and promotes its degradation. Mechanistically, this process is mediated by the viral papain-like protease (PLpro) and the proteasome. Together, these results demonstrate that DAXX restricts SARS-CoV-2, which in turn has evolved a mechanism to counteract its action.

Suggested Citation

  • Alice Mac Kain & Ghizlane Maarifi & Sophie-Marie Aicher & Nathalie Arhel & Artem Baidaliuk & Sandie Munier & Flora Donati & Thomas Vallet & Quang Dinh Tran & Alexandra Hardy & Maxime Chazal & François, 2022. "Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30134-9
    DOI: 10.1038/s41467-022-30134-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30134-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-30134-9?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. Liangqian Huang & Trisha Agrawal & Guixin Zhu & Sixiang Yu & Liming Tao & JiaBei Lin & Ronen Marmorstein & James Shorter & Xiaolu Yang, 2021. "DAXX represents a new type of protein-folding enabler," Nature, Nature, vol. 597(7874), pages 132-137, September.
    2. Donghyuk Shin & Rukmini Mukherjee & Diana Grewe & Denisa Bojkova & Kheewoong Baek & Anshu Bhattacharya & Laura Schulz & Marek Widera & Ahmad Reza Mehdipour & Georg Tascher & Paul P. Geurink & Alexande, 2020. "Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity," Nature, Nature, vol. 587(7835), pages 657-662, November.
    3. Alexis J. Combes & Tristan Courau & Nicholas F. Kuhn & Kenneth H. Hu & Arja Ray & William S. Chen & Nayvin W. Chew & Simon J. Cleary & Divyashree Kushnoor & Gabriella C. Reeder & Alan Shen & Jessica T, 2021. "Global absence and targeting of protective immune states in severe COVID-19," Nature, Nature, vol. 591(7848), pages 124-130, March.
    4. Alexis J. Combes & Tristan Courau & Nicholas F. Kuhn & Kenneth H. Hu & Arja Ray & William S. Chen & Nayvin W. Chew & Simon J. Cleary & Divyashree Kushnoor & Gabriella C. Reeder & Alan Shen & Jessica T, 2021. "Publisher Correction: Global absence and targeting of protective immune states in severe COVID-19," Nature, Nature, vol. 596(7872), pages 8-8, August.
    Full references (including those not matched with items on IDEAS)

    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. Jillian R. Jaycox & Carolina Lucas & Inci Yildirim & Yile Dai & Eric Y. Wang & Valter Monteiro & Sandra Lord & Jeffrey Carlin & Mariko Kita & Jane H. Buckner & Shuangge Ma & Melissa Campbell & Albert , 2023. "SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    2. Lucile P. A. Neyton & Ravi K. Patel & Aartik Sarma & Andrew Willmore & Sidney C. Haller & Kirsten N. Kangelaris & Walter L. Eckalbar & David J. Erle & Matthew F. Krummel & Carolyn M. Hendrickson & Pre, 2024. "Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Quy Xiao Xuan Lin & Deepa Rajagopalan & Akshamal M. Gamage & Le Min Tan & Prasanna Nori Venkatesh & Wharton O. Y. Chan & Dilip Kumar & Ragini Agrawal & Yao Chen & Siew-Wai Fong & Amit Singh & Louisa J, 2024. "Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Elvira Mennillo & Yang Joon Kim & Gyehyun Lee & Iulia Rusu & Ravi K. Patel & Leah C. Dorman & Emily Flynn & Stephanie Li & Jared L. Bain & Christopher Andersen & Arjun Rao & Stanley Tamaki & Jessica T, 2024. "Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Kami Pekayvaz & Alexander Leunig & Rainer Kaiser & Markus Joppich & Sophia Brambs & Aleksandar Janjic & Oliver Popp & Daniel Nixdorf & Valeria Fumagalli & Nora Schmidt & Vivien Polewka & Afra Anjum & , 2022. "Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    6. Yvonne M. Mueller & Thijs J. Schrama & Rik Ruijten & Marco W. J. Schreurs & Dwin G. B. Grashof & Harmen J. G. van de Werken & Giovanna Jona Lasinio & Daniel Álvarez-Sierra & Caoimhe H. Kiernan & Melis, 2022. "Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Nicolaj S. Hackert & Felix A. Radtke & Tarik Exner & Hanns-Martin Lorenz & Carsten Müller-Tidow & Peter A. Nigrovic & Guido Wabnitz & Ricardo Grieshaber-Bouyer, 2023. "Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Nik Franko & Ana Palma Teixeira & Shuai Xue & Ghislaine Charpin-El Hamri & Martin Fussenegger, 2021. "Design of modular autoproteolytic gene switches responsive to anti-coronavirus drug candidates," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    9. Mohammad Afsar & GuanQun Liu & Lijia Jia & Eliza A. Ruben & Digant Nayak & Zuberwasim Sayyad & Priscila dos Santos Bury & Kristin E. Cano & Anindita Nayak & Xiang Ru Zhao & Ankita Shukla & Patrick Sun, 2023. "Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Iqbal Mahmud & Guimei Tian & Jia Wang & Tarun E. Hutchinson & Brandon J. Kim & Nikee Awasthee & Seth Hale & Chengcheng Meng & Allison Moore & Liming Zhao & Jessica E. Lewis & Aaron Waddell & Shangtao , 2023. "DAXX drives de novo lipogenesis and contributes to tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Sara Sunshine & Andreas S. Puschnik & Joseph M. Replogle & Matthew T. Laurie & Jamin Liu & Beth Shoshana Zha & James K. Nuñez & Janie R. Byrum & Aidan H. McMorrow & Matthew B. Frieman & Juliane Winkle, 2023. "Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Pawel M. Wydorski & Jerzy Osipiuk & Benjamin T. Lanham & Christine Tesar & Michael Endres & Elizabeth Engle & Robert Jedrzejczak & Vishruth Mullapudi & Karolina Michalska & Krzysztof Fidelis & David F, 2023. "Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Xinyu Wu & Margareta Go & Julie V. Nguyen & Nathan W. Kuchel & Bernadine G. C. Lu & Kathleen Zeglinski & Kym N. Lowes & Dale J. Calleja & Jeffrey P. Mitchell & Guillaume Lessene & David Komander & Mat, 2024. "Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Sheng Chen & Anuradhika Puri & Braxton Bell & Joseph Fritsche & Hector H. Palacios & Maurie Balch & Macy L. Sprunger & Matthew K. Howard & Jeremy J. Ryan & Jessica N. Haines & Gary J. Patti & Albert A, 2024. "HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Maria I. Freiberger & Victoria Ruiz-Serra & Camila Pontes & Miguel Romero-Durana & Pablo Galaz-Davison & Cesar A. Ramírez-Sarmiento & Claudio D. Schuster & Marcelo A. Marti & Peter G. Wolynes & Diego , 2023. "Local energetic frustration conservation in protein families and superfamilies," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Jolien Van Cleemput & Willem van Snippenberg & Laurens Lambrechts & Amélie Dendooven & Valentino D’Onofrio & Liesbeth Couck & Wim Trypsteen & Jan Vanrusselt & Sebastiaan Theuns & Nick Vereecke & Thier, 2021. "Organ-specific genome diversity of replication-competent SARS-CoV-2," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    17. Iona Wallace & Kheewoong Baek & J. Rajan Prabu & Ronnald Vollrath & Susanne Gronau & Brenda A. Schulman & Kirby N. Swatek, 2023. "Insights into the ISG15 transfer cascade by the UBE1L activating enzyme," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    18. Nitish Gulve & Chenhe Su & Zhong Deng & Samantha S. Soldan & Olga Vladimirova & Jayamanna Wickramasinghe & Hongwu Zheng & Andrew V. Kossenkov & Paul. M. Lieberman, 2022. "DAXX-ATRX regulation of p53 chromatin binding and DNA damage response," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    19. 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.
    20. Benoît Arragain & Tim Krischuns & Martin Pelosse & Petra Drncova & Martin Blackledge & Nadia Naffakh & Stephen Cusack, 2024. "Structures of influenza A and B replication complexes give insight into avian to human host adaptation and reveal a role of ANP32 as an electrostatic chaperone for the apo-polymerase," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:13:y:2022:i:1:d:10.1038_s41467-022-30134-9. 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.