Evolution of naturally arising SARS-CoV-2 defective interfering particles

Samer Girgis; Zaikun Xu; Spyros Oikonomopoulos; Alla D. Fedorova; Egor P. Tchesnokov; Calvin J. Gordon; T. Martin Schmeing; Matthias Götte; Nahum Sonenberg; Pavel V. Baranov; Jiannis Ragoussis; Tom C. Hobman; Jerry Pelletier

doi:10.1038/s42003-022-04058-5

Evolution of naturally arising SARS-CoV-2 defective interfering particles

Samer Girgis
, Zaikun Xu
, Spyros Oikonomopoulos
, Alla D. Fedorova
, Egor P. Tchesnokov
, Calvin J. Gordon
, T. Martin Schmeing
, Matthias Götte
, Nahum Sonenberg
, Pavel V. Baranov
, Jiannis Ragoussis
, Tom C. Hobman
, Jerry Pelletier

School of Biochemistry and Cell Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1140
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-04058-5
Publication status	Published - Dec 2022

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10.1038/s42003-022-04058-5

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title = "Evolution of naturally arising SARS-CoV-2 defective interfering particles",

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 \textasciitilde{}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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doi = "10.1038/s42003-022-04058-5",

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AU - Girgis, Samer

AU - Xu, Zaikun

AU - Oikonomopoulos, Spyros

AU - Fedorova, Alla D.

AU - Tchesnokov, Egor P.

AU - Gordon, Calvin J.

AU - Schmeing, T. Martin

AU - Götte, Matthias

AU - Sonenberg, Nahum

AU - Baranov, Pavel V.

AU - Ragoussis, Jiannis

AU - Hobman, Tom C.

AU - Pelletier, Jerry

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85140734335

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DO - 10.1038/s42003-022-04058-5

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SN - 2399-3642

VL - 5

JO - Communications Biology

JF - Communications Biology

IS - 1

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ER -

Evolution of naturally arising SARS-CoV-2 defective interfering particles

Abstract

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