Respiratory syncytial virus (RSV) is the leading cause of acute respiratory illness (ARI) morbidity and mortality among children, and contributes significantly to illness and death in the immunocompromised, those with co-morbidities and the elderly.
Working in concert with the sequencing technology core, we will obtain the full-length RSV genomes, virome and metagenome data from respiratory specimens collected from individuals participating in three distinct studies. The first study consists of hematopoietic stem cell transplant adults acutely infected with RSV, the second study consists of children 0-18 years with an ARI requiring an outpatient or hospital visit, and the third study is the first phase-III RSV F vaccine trail in healthy pregnant women to protect their newborn infants.
From these studies, we will create RSV genomic signatures and link the viral signatures to disease severity in these unique populations. We will determine the phylodynamic evolution of key antigenic domains including B and T cell epitopes of RSV over time and by geographic regions. In viral negative respiratory samples, we will search for common respiratory pathogens missed by PCR or new viral taxa. Using the metagenomics data, we will determine if microbiota and/or virome profiles are associated with severe disease state, or specific age or immune status. RSV positive samples with unique viral gene signatures will be grown in cell systems for pathogenicity studies including human lung organoid systems available from the Organoid and Minibioreactor Array Cultivation Core. Viral kinetics, viral gene expression patterns, and host cellular responses to infection and gene expression patterns will be determined in continuous, primary and human lung organoid cell lines.
This integrated analyses of RSV genomes, microbiome, virome coupled with functional studies in cell culture systems will enhance our understanding on the dynamic evolution of RSV and its contribution to disease.