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SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells

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Title: SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells
Authors: Sasaki, Michihito Browse this author →KAKEN DB
Uemura, Kentaro Browse this author
Sato, Akihiko Browse this author
Toba, Shinsuke Browse this author
Sanaki, Takao Browse this author
Maenaka, Katsumi Browse this author →KAKEN DB
Hall, William W Browse this author
Orba, Yasuko Browse this author →KAKEN DB
Sawa, Hirofumi Browse this author →KAKEN DB
Issue Date: Jan-2021
Publisher: PLOS
Journal Title: PLoS pathogens
Volume: 17
Issue: 1
Start Page: e1009233
Publisher DOI: 10.1371/journal.ppat.1009233
PMID: 33476327
Abstract: The spike (S) protein of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which facilitates viral entry. A polybasic motif detected at the cleavage site of the S protein has been shown to broaden the cell tropism and transmissibility of the virus. Here we examine the properties of SARS-CoV-2 variants with mutations at the S protein cleavage site that undergo inefficient proteolytic cleavage. Virus variants with S gene mutations generated smaller plaques and exhibited a more limited range of cell tropism compared to the wild-type strain. These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells. Our study demonstrated that the S protein polybasic cleavage motif is a critical factor underlying SARS-CoV-2 entry and cell tropism. As such, researchers should be alert to the possibility of de novo S gene mutations emerging in tissue-culture propagated virus strains.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 佐々木 道仁

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