Defective viral genomes determine respiratory syncytial virus disease severity in children and adults

Respiratory syncytial virus (RSV) is an important cause for respiratory illness in children, immunosuppressed adults, and elderly. The outcomes of RSV vary, ranging from no symptoms, mild cold like symptoms, bronchiolitis, wheezing, and even death. Factors determining the disease severity are largely unknown. In this study, we propose copy-back DVGs (cbDVGs) are an additional viral factor that impacts RSV disease severity. cbDVGs are the truncated forms of viral genomes generated during viral replication and they suppress the standard viral replication by directly competing viral machinery and stimulating antiviral responses. Here we analyzed the cbDVG abundance and species in RSV MEMPHIS stock, which is the stock used to inoculate healthy adults in one longitudinal cohort. The abundance and species of RSV MEMPHIS stock were then compared to the lab used RSV stock enriched with cbDVGs, named RSV-HD.