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Evolution of naturally arising SARS-CoV-2 defective interfering particles.
Girgis, Samer; Xu, Zaikun; Oikonomopoulos, Spyros; Fedorova, Alla D; Tchesnokov, Egor P; Gordon, Calvin J; Schmeing, T Martin; Götte, Matthias; Sonenberg, Nahum; Baranov, Pavel V; Ragoussis, Jiannis; Hobman, Tom C; Pelletier, Jerry.
  • Girgis S; Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
  • Xu Z; Department of Cell Biology, U Alberta, Edmonton, AB, T6G 2H7, Canada.
  • Oikonomopoulos S; McGill Genome Centre, Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Fedorova AD; School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
  • Tchesnokov EP; SFI Centre for Research Training in Genomics Data Science, University College Cork, Cork, Ireland.
  • Gordon CJ; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
  • Schmeing TM; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
  • Götte M; Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
  • Sonenberg N; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
  • Baranov PV; Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
  • Ragoussis J; Rosalind and Morris Goodman Cancer Institute, Montreal, QC, H3A 1A3, Canada.
  • Hobman TC; School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
  • Pelletier J; McGill Genome Centre, Department of Human Genetics, McGill University, Montreal, QC, Canada.
Commun Biol ; 5(1): 1140, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2087322
ABSTRACT
Defective interfering (DI) particles arise during virus propagation, are conditional on parental virus for replication and packaging, and interfere with viral expansion. There is much interest in developing DIs as anti-viral agents. Here we characterize DI particles that arose following serial passaging of SARS-CoV-2 at high multiplicity of infection. The prominent DIs identified have lost ~84% of the SARS-CoV-2 genome and are capable of attenuating parental viral titers. Synthetic variants of the DI genomes also interfere with infection and can be used as conditional, gene delivery vehicles. In addition, the DI genomes encode an Nsp1-10 fusion protein capable of attenuating viral replication. These results identify naturally selected defective viral genomes that emerged and stably propagated in the presence of parental virus.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Defective Viruses / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-04058-5

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Defective Viruses / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-04058-5