Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2

Liu, Z; Zheng, H; Lin, H; Li, M; Yuan, R; Peng, J; Xiong, Q; Sun, J; Li, B; Wu, J; Yi, L; Peng, X; Zhang, H; Zhang, W; Hulswit, R J G; Loman, N; Rambaut, A; Ke, C; Bowden, T A; Pybus, O G; Lu, J; Pfeiffer, J K

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in December 2019. Notable features that make SARS-CoV-2 distinct from most other previously identified betacoronaviruses include a receptor binding domain and a unique insertion of 12 nucleotides or 4 amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells; however, the deletion of QTQTN may restrict late-phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and 12 of 24 in vitro-isolated viruses, while the deletion of NSPRRAR was identified in 3 in vitro-isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo; (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage; and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro. These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here.

Citation

Liu, Z., Zheng, H., Lin, H., Li, M., Yuan, R., Peng, J., Xiong, Q., Sun, J., Li, B., Wu, J., Yi, L., Peng, X., Zhang, H., Zhang, W., Hulswit, R. J. G., Loman, N., Rambaut, A., Ke, C., Bowden, T. A., Pybus, O. G., …Pfeiffer, J. K. (2020). Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2. Journal of Virology, 94(17),

• Journal Article Type: Article
• Acceptance Date: Jun 16, 2020
• Publication Date: Aug 17, 2020
• Deposit Date: Sep 7, 2020
• Publicly Available Date: Feb 18, 2021
• Journal: Journal of Virology
• Print ISSN: 0022-538X
• Electronic ISSN: 1098-5514
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 94
• Issue: 17
• Public URL: https://rvc-repository.worktribe.com/output/1376075
• Publisher URL: https://doi.org/10.1128/JVI.00790-20