Mechanisms of defective viral genomes generation during respiratory syncytial virus infection
Yan Sun, PhD
Department of Microbiology and Immunology
University of Rochester Medical Center
Defective Viral Genomes (DVGs) are truncated forms of viral genomes that lack the ability to complete replication unless complemented with a homologous helper virus. They are produced during infection with most RNA viruses and they play a critical role in viral pathogenesis. For example, they can reduce the viral load by triggering strong innate immune responses and interfering with full-length viral genome replication. They also facilitate the establishment of viral persistence. While DVGs are important, we
don’t know how they arise. The major goal of our research is to understand the molecular mechanisms and determining factors of DVG generation. We use Respiratory Syncytial Virus (RSV) to study this topic in human, since it is an important human pathogen that causes severe problems in infants, immunocompromised adults, and the elderly. It is a leading cause of respiratory illness in children worldwide. RSV generates copy-back type of DVGs (cbDVGs) when the viral polymerase falls off the template and reattaches to the newly synthesized strand, forming a theoretical hairpin loop structure. cbDVGs are observed in RSV infection in vitro, in vivo, and in patients. Our previous studies show that their kinetics critically impact RSV disease severity. In order to study cbDVG generation during RSV infection, we developed an algorithm to survey entire cbDVG populations from RNA-seq dataset. To our surprise, we found that despite vast variation in cbDVG species among different RSV infections, cbDVG generation is concentrated in certain genomic hotspots and can be directed by certain mutations within hotspots. We are interested in further understanding the mechanism of how these hotspots regulate cbDVG generation during RSV infection. Furthermore, as DVGs can be generated universally, we are seeking the function and generation mechanism of SARS-CoV-2 DVGs. We think understanding those factors, and eventually taking advantage of them will allow us to better mitigate virally induced pathology.
Thursday, September 16, 2021 at 12:00 p.m.
Meeting URL: https://illinois.zoom.us/j/86180151648?pwd=S0lTSVl0VWV1TmZtOXYvQW9yT081QT09
Meeting ID: 861 8015 1648
For more information contact the Department of Pathobiology at 217-333-2449, email firstname.lastname@example.org.