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

tetano

Editor, Senior Moderator
Cell Discov


. 2021 Dec 14;7(1):119.
doi: 10.1038/s41421-021-00357-z.
SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells


Jinliang Wang[SUP] #[/SUP][SUP] 1 [/SUP], Guan Yang[SUP] #[/SUP][SUP] 2 [/SUP], Xinxin Wang[SUP] #[/SUP][SUP] 1 [/SUP], Zhiyuan Wen[SUP] 1 [/SUP], Lei Shuai[SUP] 1 [/SUP], Jie Luo[SUP] 1 [/SUP], Chong Wang[SUP] 1 [/SUP], Ziruo Sun[SUP] 1 [/SUP], Renqiang Liu[SUP] 1 [/SUP], Jinying Ge[SUP] 1 [/SUP], Xijun He[SUP] 1 [/SUP], Ronghong Hua[SUP] 1 [/SUP], Xijun Wang[SUP] 1 [/SUP], Xiao Yang[SUP] 2 [/SUP], Weiye Chen[SUP] 1 [/SUP], Gongxun Zhong[SUP] 1 [/SUP], Zhigao Bu[SUP] 3 [/SUP]



Affiliations

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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