PhD defence Ilaria Manfredonia

Hidden in the fold
Structural complexity and functional versatility in the genomes of RNA viruses
Hidden in the fold: structural complexity and functional versatility in the genomes of RNA viruses. Like a Swiss-army knife, RNA virus genomes pack an astonishing range of functions into a tiny space. Understanding how requires looking beyond the protein-coding sequence to other features that may regulate the virus, such as the 3D shapes RNA folds into. This thesis first mapped the SARS-CoV-2 genome base by base to identify structures crucial to the virus, which could serve as new drug targets. RNA structures were then compared across the genomes of orthoflaviviruses (such as dengue and Zika), showing that conserved shapes can reveal evolutionary history that the genetic sequence alone does not. Finally, polycipiviruses were tracked in wild garden ant colonies in the Netherlands, showing that viruses can persist in their hosts without visible disease and highlighting the value of studying viruses in nature to contextualize their ecology and evolution. Take-home message: RNA is not a passive carrier of genetic information but a primary engine of viral resilience and adaptability.