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Patient-derived SARS-CoV-2 mutations impact viral replication dynamics and infectivity in vitro and with clinical implications in vivo.
Yao, Hangping; Lu, Xiangyun; Chen, Qiong; Xu, Kaijin; Chen, Yu; Cheng, Minghui; Chen, Keda; Cheng, Linfang; Weng, Tianhao; Shi, Danrong; Liu, Fumin; Wu, Zhigang; Xie, Mingjie; Wu, Haibo; Jin, Changzhong; Zheng, Min; Wu, Nanping; Jiang, Chao; Li, Lanjuan.
  • Yao H; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Lu X; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Chen Q; Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, 310012, China.
  • Xu K; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Chen Y; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Cheng M; Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, 310012, China.
  • Chen K; Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, 310015, China.
  • Cheng L; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Weng T; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Shi D; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Liu F; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Wu Z; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Xie M; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Wu H; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Jin C; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
  • Zheng M; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China. minzheng@zju.edu.cn.
  • Wu N; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China. flwnp2013@163.com.
  • Jiang C; Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, 310012, China. jiang_chao@zju.edu.cn.
  • Li L; Zhejiang Provincial Key Laboratory of Pancreatic Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China. jiang_chao@zju.edu.cn.
Cell Discov ; 6(1): 76, 2020 Oct 29.
Article in English | MEDLINE | ID: covidwho-904771
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with more than 33 million patients diagnosed, taking more than a million lives. Abundant mutations were observed but the functional consequences of these mutations are largely unknown. We report the mutation spectrum, replication dynamics, and infectivity of 11 patient-derived viral isolates in diverse cell lines, including the human lung cancer cell line Calu-3. We observed 46 mutations, including 9 different mutations in the spike gene. Importantly, these viral isolates show significant and consistent variations in replication dynamics and infectivity in tested cell lines, up to a 1500-fold difference in viral titers at 24 h after infecting Calu-3 cells. Moreover, we show that the variations in viral titers among viral isolates are positively correlated with blood clotting function but inversely correlated with the amount of red blood cell and hemoglobin in patients. Therefore, we provide direct evidence that naturally occurring mutations in SARS-CoV-2 can substantially change its replication dynamics and infectivity in diverse human cell lines, with clinical implications in vivo.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Journal: Cell Discov Year: 2020 Document Type: Article Affiliation country: S41421-020-00226-1

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Journal: Cell Discov Year: 2020 Document Type: Article Affiliation country: S41421-020-00226-1