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

Nat Commun. 2020 Aug 4;11(1):3896. doi: 10.1038/s41467-020-17638-y.

Mayank Srivastava ^# ¹, Ying Zhang ^# ² ³, Jian Chen ^# ⁴, Devika Sirohi ⁵ ⁶, Andrew Miller ⁵ ⁶, Yang Zhang ⁷, Zhilu Chen ⁷ ⁴, Haojie Lu ⁷, Jianqing Xu ⁸ ⁹, Richard J Kuhn ¹⁰ ¹¹, W Andy Tao ¹² ¹³ ¹⁴

Affiliations

1 Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
2 Institutes of Biomedical Sciences and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai, 200032, China. [email protected].
3 Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
4 Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200032, China.
5 Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
6 Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, 47907, USA.
7 Institutes of Biomedical Sciences and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai, 200032, China.
8 Institutes of Biomedical Sciences and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai, 200032, China. [email protected].
9 Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200032, China. [email protected].
10 Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
11 Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
12 Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
13 Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
14 Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
# Contributed equally.

PMID: 32753727 DOI: 10.1038/s41467-020-17638-y

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.