IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44175-1.html
   My bibliography  Save this article

Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection

Author

Listed:
  • Jiakai Hou

    (University of Houston)

  • Yanjun Wei

    (The University of Texas MD Anderson Cancer Center)

  • Jing Zou

    (The University of Texas Medical Branch)

  • Roshni Jaffery

    (University of Houston)

  • Long Sun

    (The University of Texas Medical Branch)

  • Shaoheng Liang

    (The University of Texas MD Anderson Cancer Center
    Rice University
    Carnegie Mellon University)

  • Ningbo Zheng

    (University of Houston)

  • Ashley M. Guerrero

    (University of Houston)

  • Nicholas A. Egan

    (University of Houston)

  • Ritu Bohat

    (University of Houston)

  • Si Chen

    (University of Houston)

  • Caishang Zheng

    (The University of Texas MD Anderson Cancer Center)

  • Xiaobo Mao

    (Johns Hopkins University School of Medicine)

  • S. Stephen Yi

    (The University of Texas at Austin
    The University of Texas at Austin)

  • Ken Chen

    (The University of Texas MD Anderson Cancer Center)

  • Daniel J. McGrail

    (Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic)

  • Nidhi Sahni

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Pei-Yong Shi

    (The University of Texas Medical Branch
    The University of Texas Medical Branch
    The University of Texas Medical Branch
    The University of Texas Medical Branch)

  • Yiwen Chen

    (The University of Texas MD Anderson Cancer Center
    Quantitative Sciences Program, MD Anderson Cancer Center, UT Health Graduate School of Biomedical Sciences)

  • Xuping Xie

    (The University of Texas Medical Branch
    The University of Texas Medical Branch)

  • Weiyi Peng

    (University of Houston)

Abstract

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discover another anti-viral regulator KLF5, a transcriptional factor involved in sphingolipid metabolism, which is up-regulated, and harbors genetic variations linked to COVID-19 patients with severe symptoms. Anti-viral effects of three identified candidates (DAZAP2/VTA1/KLF5) are confirmed individually. Molecular characterization of DAZAP2/VTA1/KLF5-knockout cells highlights the involvement of genes related to the coagulation system in determining the severity of COVID-19. Together, our results provide further resources for understanding the host anti-viral network during SARS-CoV-2 infection and may help develop new countermeasure strategies.

Suggested Citation

  • Jiakai Hou & Yanjun Wei & Jing Zou & Roshni Jaffery & Long Sun & Shaoheng Liang & Ningbo Zheng & Ashley M. Guerrero & Nicholas A. Egan & Ritu Bohat & Si Chen & Caishang Zheng & Xiaobo Mao & S. Stephen, 2024. "Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44175-1
    DOI: 10.1038/s41467-023-44175-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44175-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44175-1?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. David E. Gordon & Gwendolyn M. Jang & Mehdi Bouhaddou & Jiewei Xu & Kirsten Obernier & Kris M. White & Matthew J. O’Meara & Veronica V. Rezelj & Jeffrey Z. Guo & Danielle L. Swaney & Tia A. Tummino & , 2020. "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing," Nature, Nature, vol. 583(7816), pages 459-468, July.
    2. Ryuichiro Nakato & Toyonori Sakata & Jiankang Wang & Luis Augusto Eijy Nagai & Yuya Nagaoka & Gina Miku Oba & Masashige Bando & Katsuhiko Shirahige, 2023. "Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Yunkai Zhu & Fei Feng & Gaowei Hu & Yuyan Wang & Yin Yu & Yuanfei Zhu & Wei Xu & Xia Cai & Zhiping Sun & Wendong Han & Rong Ye & Di Qu & Qiang Ding & Xinxin Huang & Hongjun Chen & Wei Xu & Youhua Xie , 2021. "A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Xuping Xie & Antonio E. Muruato & Xianwen Zhang & Kumari G. Lokugamage & Camila R. Fontes-Garfias & Jing Zou & Jianying Liu & Ping Ren & Mini Balakrishnan & Tomas Cihlar & Chien-Te K. Tseng & Shinji M, 2020. "A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    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. Ma’ayan Israeli & Yaara Finkel & Yfat Yahalom-Ronen & Nir Paran & Theodor Chitlaru & Ofir Israeli & Inbar Cohen-Gihon & Moshe Aftalion & Reut Falach & Shahar Rotem & Uri Elia & Ital Nemet & Limor Klik, 2022. "Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. David Gomez-Zepeda & Danielle Arnold-Schild & Julian Beyrle & Arthur Declercq & Ralf Gabriels & Elena Kumm & Annica Preikschat & Mateusz Krzysztof Łącki & Aurélie Hirschler & Jeewan Babu Rijal & Chris, 2024. "Thunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by MS2Rescore with MS2PIP timsTOF fragmentation prediction model," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Christine E. Peters & Ursula Schulze-Gahmen & Manon Eckhardt & Gwendolyn M. Jang & Jiewei Xu & Ernst H. Pulido & Conner Bardine & Charles S. Craik & Melanie Ott & Or Gozani & Kliment A. Verba & Ruth H, 2022. "Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Gabriela Dias Noske & Yun Song & Rafaela Sachetto Fernandes & Rod Chalk & Haitem Elmassoudi & Lizbé Koekemoer & C. David Owen & Tarick J. El-Baba & Carol V. Robinson & Glaucius Oliva & Andre Schutzer , 2023. "An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Haofeng Wang & Qi Yang & Xiaoce Liu & Zili Xu & Maolin Shao & Dongxu Li & Yinkai Duan & Jielin Tang & Xianqiang Yu & Yumin Zhang & Aihua Hao & Yajie Wang & Jie Chen & Chenghao Zhu & Luke Guddat & Hong, 2023. "Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. 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.
    8. Xiaopan Gao & Huabin Tian & Kaixiang Zhu & Qing Li & Wei Hao & Linyue Wang & Bo Qin & Hongyu Deng & Sheng Cui, 2022. "Structural basis for Sarbecovirus ORF6 mediated blockage of nucleocytoplasmic transport," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    9. Thomas Kruse & Caroline Benz & Dimitriya H. Garvanska & Richard Lindqvist & Filip Mihalic & Fabian Coscia & Raviteja Inturi & Ahmed Sayadi & Leandro Simonetti & Emma Nilsson & Muhammad Ali & Johanna K, 2021. "Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    10. Filip Mihalič & Leandro Simonetti & Girolamo Giudice & Marie Rubin Sander & Richard Lindqvist & Marie Berit Akpiroro Peters & Caroline Benz & Eszter Kassa & Dilip Badgujar & Raviteja Inturi & Muhammad, 2023. "Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Hanbaek Lyu & Yacoub H. Kureh & Joshua Vendrow & Mason A. Porter, 2024. "Learning low-rank latent mesoscale structures in networks," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    12. Yang Liu & Xianwen Zhang & Jianying Liu & Hongjie Xia & Jing Zou & Antonio E. Muruato & Sivakumar Periasamy & Chaitanya Kurhade & Jessica A. Plante & Nathen E. Bopp & Birte Kalveram & Alexander Bukrey, 2022. "A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    13. Charulata Jindal & Sandeep Kumar & Sunil Sharma & Yuk Ming Choi & Jimmy T. Efird, 2020. "The Prevention and Management of COVID-19: Seeking a Practical and Timely Solution," IJERPH, MDPI, vol. 17(11), pages 1-11, June.
    14. Kelsey M. Haas & Michael J. McGregor & Mehdi Bouhaddou & Benjamin J. Polacco & Eun-Young Kim & Thong T. Nguyen & Billy W. Newton & Matthew Urbanowski & Heejin Kim & Michael A. P. Williams & Veronica V, 2023. "Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    15. Filip Mihalič & Caroline Benz & Eszter Kassa & Richard Lindqvist & Leandro Simonetti & Raviteja Inturi & Hanna Aronsson & Eva Andersson & Celestine N. Chi & Norman E. Davey & Anna K. Överby & Per Jemt, 2023. "Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    16. Pisanu Buphamalai & Tomislav Kokotovic & Vanja Nagy & Jörg Menche, 2021. "Network analysis reveals rare disease signatures across multiple levels of biological organization," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    17. Daniel Strebinger & Chris J. Frangieh & Mirco J. Friedrich & Guilhem Faure & Rhiannon K. Macrae & Feng Zhang, 2023. "Cell type-specific delivery by modular envelope design," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    18. 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.
    19. Joseph Hiatt & Judd F. Hultquist & Michael J. McGregor & Mehdi Bouhaddou & Ryan T. Leenay & Lacy M. Simons & Janet M. Young & Paige Haas & Theodore L. Roth & Victoria Tobin & Jason A. Wojcechowskyj & , 2022. "A functional map of HIV-host interactions in primary human T cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Kshitiz Walia & Abhishek Sharma & Sankalita Paul & Priya Chouhan & Gaurav Kumar & Rajesh Ringe & Mahak Sharma & Amit Tuli, 2024. "SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle," Nature Communications, Nature, vol. 15(1), pages 1-24, 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:15:y:2024:i:1:d:10.1038_s41467-023-44175-1. 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.