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A trans-complementation system for SARS-CoV-2 recapitulates authentic viral replication without virulence.
Zhang, Xianwen; Liu, Yang; Liu, Jianying; Bailey, Adam L; Plante, Kenneth S; Plante, Jessica A; Zou, Jing; Xia, Hongjie; Bopp, Nathen E; Aguilar, Patricia V; Ren, Ping; Menachery, Vineet D; Diamond, Michael S; Weaver, Scott C; Xie, Xuping; Shi, Pei-Yong.
  • Zhang X; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Liu Y; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Liu J; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
  • Bailey AL; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Plante KS; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Gal
  • Plante JA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Gal
  • Zou J; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Xia H; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • Bopp NE; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Aguilar PV; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Ren P; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • Menachery VD; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
  • Diamond MS; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  • Weaver SC; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Gal
  • Xie X; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: xuxie@UTMB.edu.
  • Shi PY; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA;
Cell ; 184(8): 2229-2238.e13, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1095902
ABSTRACT
The biosafety level 3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research. Here, we report a trans-complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans-complementation system consists of two components a genomic viral RNA containing ORF3 and envelope gene deletions, as well as mutated transcriptional regulator sequences, and a producer cell line expressing the two deleted genes. Trans-complementation of the two components generates virions that can infect naive cells for only one round but does not produce wild-type SARS-CoV-2. Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. Thus, the trans-complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Containment of Biohazards / SARS-CoV-2 / COVID-19 Limits: Animals / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.02.044

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Containment of Biohazards / SARS-CoV-2 / COVID-19 Limits: Animals / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.02.044