SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells

  • Cell Discov. 2021 Dec 14;7(1):119. doi: 10.1038/s41421-021-00357-z.
Jinliang Wang   #  1 ,  Guan Yang   #  2 ,  Xinxin Wang   #  1 ,  Zhiyuan Wen  1 ,  Lei Shuai  1 ,  Jie Luo  1 ,  Chong Wang  1 ,  Ziruo Sun  1 ,  Renqiang Liu  1 ,  Jinying Ge  1 ,  Xijun He  1 ,  Ronghong Hua  1 ,  Xijun Wang  1 ,  Xiao Yang  2 ,  Weiye Chen  1 ,  Gongxun Zhong  1 ,  Zhigao Bu  3
Affiliations
  • 1. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China.
  • 2. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
  • 3. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. [email protected].
  • # Contributed equally.
PMID: 34903715 DOI: 10.1038/s41421-021-00357-z
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) as a binding receptor to enter cells via clathrin-mediated endocytosis (CME). However, receptors involved in other steps of SARS-CoV-2 Infection remain largely unknown. Here, we found that metabotropic glutamate receptor subtype 2 (mGluR2) is an internalization factor for SARS-CoV-2. Our results show that mGluR2 directly interacts with the SARS-CoV-2 spike protein and that knockdown of mGluR2 decreases internalization of SARS-CoV-2 but not cell binding. Further, mGluR2 is uncovered to cooperate with ACE2 to facilitate SARS-CoV-2 internalization through CME and mGluR2 knockout in mice abolished SARS-CoV-2 Infection in the nasal turbinates and significantly reduced Viral Infection in the Lungs. Notably, mGluR2 is also important for SARS-CoV spike protein- and Middle East respiratory syndrome coronavirus spike protein-mediated internalization. Thus, our study identifies a novel internalization factor used by SARS-CoV-2 and opens a new door for Antiviral development against Coronavirus Infection.

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