Viral evasion of cell intrinsic innate immune responses
Navn på bevillingshaver
Troels Scheel
Institution
University of Copenhagen
Beløb
DKK 4,991,510
År
2021
Bevillingstype
Semper Ardens: Accelerate
Hvad?
Viral infections have severe impact on human health, including novel outbreaks of disease like COVID-19. To detect and combat the virus, the infected cell is equipped with a number of intrinsic innate immune defense strategies. Viruses on the other hand attempt to evade detection and counteract the cellular responses. This project focuses on identifying and characterizing novel mechanisms of viral evasion and counteracting of cellular immune responses. Understanding the arms race between our cells and the pathogens that challenge them gives us important insights to pathology and ways to combat infections.
Hvorfor?
Our cells continuously survey for unusual molecular patterns suggesting viral infection. To avoid recognition, viruses employ various strategies to hide from the recognition machinery or by mimicking normal cellular molecules. Our knowledge of how in particular viruses with RNA genomes protect themselves from recognition remains incomplete. This study could provide better insight to cellular recognition of viral RNA and of viral protection mechanisms. Viruses in addition encode proteins that work to counteract the cellular responses and such constitute potential antiviral targets. We have knowledge of many such proteins, but a systematic mapping has not been done.
Hvordan?
Viruses with RNA genomes face a particular challenge in avoiding recognition given particular structures and forms not present in cellular RNA. This project studies novel ways that viruses protect and cap their RNA from being sensed by the cellular machinery. To provide a more comprehensive understanding of viral factors that counteract cell intrinsic immunity, we have further devised an innovative platform where genes from hundreds of pathogenic viruses can be screened for their ability to block intracellular immune signaling. This could educate us on novel viral points of immune intervention, but could also identify novel putative antiviral targets.