SARS-CoV-2 Defective Interfering Particles

Coronaviruses show high rates of recombination which leads to the generation of defective viral genomes (DVGs). The vast majority of DVGs represent dead-end products as they lack essential cis-acting elements for replication or packaging. However, under appropriate propagation conditions (i.e., high multiplicity of infection [moi]), DVGs can emerge that have lost significant coding potential yet retain the ability to propagate in the presence of parental virus. These DVGs attenuate viral titers by competing with the parental virus for limiting resources and have been coined defective interfering (DI) particles. We isolated DIs arising from serially passaged SARS-CoV-2 and present their genetic and functional characterization. The SARS-CoV-2 DI genomes encoded a novel Nsp1-10 fusion protein and behave as DIs to attenuate viral replication. Synthetic variants of SARS-CoV-2 DI genomes can be engineered as conditional, gene delivery vehicles.