SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells #MMPMID34903715
Wang J; Yang G; Wang X; Wen Z; Shuai L; Luo J; Wang C; Sun Z; Liu R; Ge J; He X; Hua R; Wang X; Yang X; Chen W; Zhong G; Bu Z
Cell Discov 2021[Dec]; 7 (1): 119 PMID34903715show ga
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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Cell+Discov 2021 ; 7 (1): 119
