IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-21213-4.html
   My bibliography  Save this article

A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry

Author

Listed:
  • Yunkai Zhu

    (Fudan University)

  • Fei Feng

    (Fudan University)

  • Gaowei Hu

    (Fudan University)

  • Yuyan Wang

    (Fudan University)

  • Yin Yu

    (Fudan University)

  • Yuanfei Zhu

    (Fudan University)

  • Wei Xu

    (Fudan University)

  • Xia Cai

    (Fudan University)

  • Zhiping Sun

    (Fudan University)

  • Wendong Han

    (Fudan University)

  • Rong Ye

    (Fudan University)

  • Di Qu

    (Fudan University)

  • Qiang Ding

    (Tsinghua University)

  • Xinxin Huang

    (Plant and Food Inspection and Quarantine of Shanghai Customs)

  • Hongjun Chen

    (CAAS)

  • Wei Xu

    (Southern Medical University)

  • Youhua Xie

    (Fudan University)

  • Qiliang Cai

    (Fudan University)

  • Zhenghong Yuan

    (Fudan University)

  • Rong Zhang

    (Fudan University)

Abstract

The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21213-4
    DOI: 10.1038/s41467-021-21213-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-21213-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-21213-4?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
    ---><---

    Citations

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


    Cited by:

    1. 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.
    2. Joseph D. Trimarco & Sarah L. Nelson & Ryan R. Chaparian & Alexandra I. Wells & Nathan B. Murray & Parastoo Azadi & Carolyn B. Coyne & Nicholas S. Heaton, 2022. "Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. 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.

    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_s41467-021-21213-4. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.