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
Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Department of Cell Biology, U Alberta, Edmonton, AB, T6G 2H7, Canada.
Commun Biol. 2022 Oct 27;5(1):1140. doi: 10.1038/s42003-022-04058-5.
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.
缺陷干扰（DI）颗粒在病毒传播过程中产生，其复制和包装依赖于亲代病毒，并会干扰病毒的扩增。人们对开发DI颗粒作为抗病毒药物很感兴趣。在此，我们对在高感染复数下连续传代的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）所产生的DI颗粒进行了表征。鉴定出的主要DI颗粒已丢失约84%的SARS-CoV-2基因组，并且能够降低亲代病毒滴度。DI基因组的合成变体也能干扰感染，可作为条件性基因传递载体。此外，DI基因组编码一种能够减弱病毒复制的Nsp1-10融合蛋白。这些结果鉴定出了在亲代病毒存在的情况下出现并稳定传播的自然选择的缺陷病毒基因组。
