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

Mayank Srivastava, Ying Zhang (), Jian Chen, Devika Sirohi, Andrew Miller, Yang Zhang, Zhilu Chen, Haojie Lu, Jianqing Xu (), Richard J. Kuhn () and W. Andy Tao ()
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Mayank Srivastava: Purdue University
Ying Zhang: Fudan University
Jian Chen: Fudan University
Devika Sirohi: Purdue University
Andrew Miller: Purdue University
Yang Zhang: Fudan University
Zhilu Chen: Fudan University
Haojie Lu: Fudan University
Jianqing Xu: Fudan University
Richard J. Kuhn: Purdue University
W. Andy Tao: Purdue University

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17638-y

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