Defective interfering (DI) genomes are truncated forms of the viral genome that are generated by most viruses during replication. Although DI genomes cannot replicate without the presence of a complete, functional viral genome, they possess immune-stimulatory properties. Due to their structural features, they can trigger type I interferon (IFN-I) signaling through the activation of cytosolic RNA sensors such as RIG-I.
DI genomes—particularly the 5′ copy-back forms (DI-RNAs)—are well characterized in paramyxoviruses. These specific DI-RNAs are produced when the viral polymerase, through a mechanism that remains unclear, detaches from the template and reattaches to copy back the 5′ end of the genome. The attenuated MV-Schwarz vaccine strain is known to be a poor producer of DI genomes. In cell culture, the generation of DI-RNAs depends on factors such as the multiplicity of infection (MOI) and the number of cell passages. However, a modification to the MV genome has been shown to enhance DI-RNA production in a modified strain.
In this project, we aim to identify and characterize DI genomes produced in various infected cell lines. We will compare cells infected with the MV-Schwarz vaccine strain to those infected with the modified strain that produces high levels of DI genomes. Additionally, we will analyze the cellular pathways that are differentially upregulated or downregulated in infected versus non-infected cells.
