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

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. Genomes from defective interfering (DI) particles following serial passaging of SARS-CoV-2 reveal a fusion protein that attenuates viral replication. Synthetic, recombinant DI genomes are designed to interfere with SARS-CoV-2 replication.

Automated summary

This study characterizes defective interfering (DI) particles generated through serial passaging of SARS-CoV-2. The identified DI particles have lost a significant portion of the SARS-CoV-2 genome and can attenuate viral replication. Synthetic variants of the DI genomes interfere with infection and can serve as gene delivery vehicles. Furthermore, the DI genomes encode a fusion protein that can attenuate viral replication.