Meta-analysis of genomic characteristics for antiviral influenza defective interfering particle prioritization

Defective interfering particles (DIPs) are viral deletion mutants that hamper virus replication and are, thus, potent novel antiviral agents. To evaluate possible antiviral treatments, we first need to get a deeper understanding of DIP characteristics. Thus, we performed a meta-analysis of 20 already published sequencing datasets of influenza A and B viruses (IAV and IBV) from in vivo and in vitro experiments. We analyzed each dataset for characteristics, such as deletion-containing viral genome (DelVG) length distributions, direct repeats, and nucleotide enrichment at the deletion site. Our analysis suggests differences in the length of the 3'- and 5'-end retained in IAV and IBV viral sequences upon deletion. Moreover, in vitro DelVGs tend to be shorter than those in vivo, which is a novel finding with potential implications for future DIP treatment design. Additionally, our analysis demonstrates the presence of DelVGs with longer than expected sequences, possibly related to an alternative mechanism of DelVG formation. Finally, a joint ranking of DelVGs originating from 7 A/Puerto Rico/8/1934 datasets revealed 11 highly abundant, yet unnoticed, candidates. Together, our study highlights the importance of meta-analyses to uncover yet unknown DelVG characteristics and to pre-select candidates for antiviral treatment design.