Proteomics

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Chemical Proteomics Tracks Virus Entry and Uncovers NCAM1 As Zika Virus Receptor

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Macaca Mulatta (rhesus Macaque)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Disease Free

SUBMITTER: Ying Zhang  

LAB HEAD: W.Andy Tao

PROVIDER: PXD020119 | Pride | 2020-09-11

REPOSITORIES: Pride

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

Srivastava Mayank M   Zhang Ying Y   Chen Jian J   Sirohi Devika D   Miller Andrew A   Zhang Yang Y   Chen Zhilu Z   Lu Haojie H   Xu Jianqing J   Kuhn Richard J RJ   Andy Tao W W  

Nature communications 20200804 1

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  ...[more]

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