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Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus receptor

Author

Listed:
  • Mayank Srivastava

    (Purdue University)

  • Ying Zhang

    (Fudan University
    Purdue University)

  • Jian Chen

    (Fudan University)

  • Devika Sirohi

    (Purdue University
    Purdue University)

  • Andrew Miller

    (Purdue University
    Purdue University)

  • Yang Zhang

    (Fudan University)

  • Zhilu Chen

    (Fudan University
    Fudan University)

  • Haojie Lu

    (Fudan University)

  • Jianqing Xu

    (Fudan University
    Fudan University)

  • Richard J. Kuhn

    (Purdue University
    Purdue University)

  • W. Andy Tao

    (Purdue University
    Purdue University
    Purdue University)

Abstract

The outbreak of Zika virus (ZIKV) in 2016 created worldwide health emergency which demand urgent research efforts on understanding the virus biology and developing therapeutic strategies. Here, we present a time-resolved chemical proteomic strategy to track the early-stage entry of ZIKV into host cells. ZIKV was labeled on its surface with a chemical probe, which carries a photocrosslinker to covalently link virus-interacting proteins in living cells on UV exposure at different time points, and a biotin tag for subsequent enrichment and mass spectrometric identification of the receptor or other host proteins critical for virus internalization. We identified Neural Cell Adhesion Molecule (NCAM1) as a potential ZIKV receptor and further validated it through overexpression, knockout, and inhibition of NCAM1 in Vero cells and human glioblastoma cells U-251 MG. Collectively, the strategy can serve as a universal tool to map virus entry pathways and uncover key interacting proteins.

Suggested Citation

  • Mayank Srivastava & Ying Zhang & Jian Chen & Devika Sirohi & Andrew Miller & Yang Zhang & Zhilu Chen & Haojie Lu & Jianqing Xu & Richard J. Kuhn & W. Andy Tao, 2020. "Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus receptor," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17638-y
    DOI: 10.1038/s41467-020-17638-y
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