Genomic, Immunologic, Transcriptional and Functional Interrogation of SARS-CoV-2 and Respiratory Syncytial Virus

SARS-CoV-2 and RSV are ubiquitous respiratory viruses, and a leading cause of morbidity and mortality globally. Despite great advances in our biological understanding of these pathogens, there remains a need for multidisciplinary research that improves diagnostics, utilizes genomic surveillance for viral variant detection, characterizes the innate and adaptive immune response to viral infections, and identifies host determinants of infection. In this dissertation, I describe the work that I have contributed to for the systematic interrogation of these aspects of SARS-CoV-2 and RSV biology. Chapters 2 through 5 describe the collaborative studies performed to evaluate a SARS-CoV-2 rapid antigen test (Chapter 2) and to investigate the humoral immune response to SARS-CoV-2 infection (Chapter 3-5). We additionally used Perturb-seq, a single-cell CRISPRi screening method, to functionally interrogate how host genetic perturbations affect SARS-CoV-2 infection dynamics (Chapter 6). The final chapter of this dissertation focuses on RSV. We characterized the transcriptional signatures of RSV infected and bystander activated cells using single-cell RNA sequencing and identified host determinants of RSV infection using a genome-wide CRISPR screening approach. Together, these chapters provide insight into multiple aspects of SARS-CoV-2 and RSV biology, and lay the groundwork for future studies