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
Affiliations
Shan-Shan Gao
Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 10000, China; 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
Run Shi
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
Jing Sun
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
Yanhong Tang
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
Zhenhua Zheng
Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China
Jing-Feng Li
Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China
Huan Li
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
Jie Zhang
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; Department of Stomatology, First Affiliated Hospital, School of Medicine, Shihezi University, No. 107 North 2nd Road, Shihezi, Xinjiang 832008, China
Qibin Leng
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
Jiang Xu
Department of Stomatology, First Affiliated Hospital, School of Medicine, Shihezi University, No. 107 North 2nd Road, Shihezi, Xinjiang 832008, China
Xinwen Chen
Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China; 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; Guangzhou Laboratory, Bioisland, Guangzhou 510320, China; Corresponding author
Jincun Zhao
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; Guangzhou Laboratory, Bioisland, Guangzhou 510320, China; Corresponding author
Man-Sun Sy
Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
Liqiang Feng
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
Chaoyang Li
Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan 430071, China; 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; Corresponding author
Summary: 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.
