GPI-anchored ligand-BioID2-tagging system identifies Galectin-1 mediating Zika virus entry

Shan-Shan Gao; Run Shi; Jing Sun; Yanhong Tang; Zhenhua Zheng; Jing-Feng Li; Huan Li; Jie Zhang; Qibin Leng; Jiang Xu; Xinwen Chen; Jincun Zhao; Man-Sun Sy; Liqiang Feng; Chaoyang Li

doi:10.1016/j.isci.2022.105481

GPI-anchored ligand-BioID2-tagging system identifies Galectin-1 mediating Zika virus entry

iScience. 2022 Nov 2;25(12):105481. doi: 10.1016/j.isci.2022.105481. eCollection 2022 Dec 22.

Authors

Shan-Shan Gao^{1

2

3}, Run Shi³, Jing Sun⁴, Yanhong Tang⁴, Zhenhua Zheng¹, Jing-Feng Li¹, Huan Li³, Jie Zhang^{3

5}, Qibin Leng³, Jiang Xu⁵, Xinwen Chen^{1

4

6}, Jincun Zhao^{4

6}, Man-Sun Sy⁷, Liqiang Feng⁸, Chaoyang Li^{1

3}

Affiliations

¹ Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China.
² University of Chinese Academy of Sciences, Beijing 10000, China.
³ Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong High Education Institute, 78 Heng Zhi Gang Road, Guangzhou 510095, China.
⁴ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China.
⁵ Department of Stomatology, First Affiliated Hospital, School of Medicine, Shihezi University, No. 107 North 2nd Road, Shihezi, Xinjiang 832008, China.
⁶ Guangzhou Laboratory, Bioisland, Guangzhou 510320, China.
⁷ Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
⁸ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

Abstract

Identification of host factors facilitating pathogen entry is critical for preventing infectious diseases. Here, we report a tagging system consisting of a viral receptor-binding protein (RBP) linked to BioID2, which is expressed on the cell surface via a GPI anchor. Using VSV or Zika virus (ZIKV) RBP, the system (BioID2- RBP(V)-GPI; BioID2-RBP(Z)-GPI) faithfully identifies LDLR and AXL, the receptors of VSV and ZIKV, respectively. Being GPI-anchored is essential for the probe to function properly. Furthermore, BioID2-RBP(Z)-GPI expressed in human neuronal progenitor cells identifies galectin-1 on cell surface pivotal for ZIKV entry. This conclusion is further supported by antibody blocking and galectin-1 silencing in A549 and mouse neural cells. Importantly, Lgals1 ^-/- mice are significantly more resistant to ZIKV infection than Lgals1 ^+/+ littermates are, having significantly lower virus titers and fewer pathologies in various organs. This tagging system may have broad applications for identifying protein-protein interactions on the cell surface.

Keywords: Biological sciences; Microbiology; Molecular biology; Virology.