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

Liu, Z and Zheng, H and Lin, H and Li, M and Yuan, R and Peng, J and Xiong, Q and Sun, J and Li, B and Wu, J and Yi, L and Peng, X and Zhang, H and Zhang, W and Hulswit, R J G and Loman, N and Rambaut, A and Ke, C and Bowden, T A and Pybus, O G and Lu, J and Pfeiffer, J K (2020) Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2. Journal of Virology, 94 (17). ISSN 0022-538X

12957_Identification of common deletions in the spike protein of SARS-CoV-2_GREEN AAM.pdf - Accepted Version
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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.

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