We study viruses with positive-sense RNA genomes, including Coronaviruses and Orthoflaviviruses. The genomes of these viruses play many roles during the lifecycle: first, they are messenger RNAs for the translation of viral proteins, then they are templates for RNA replication and transcription, and finally they are packaged into virus particles to transmit this genetic information to new host cells. These processes are tightly regulated to ensure efficient replication and to avoid alerting the host innate immune response.
Genome packaging
Coronavirus and flavivirus particles are made up of an RNA molecule, which carries the genetic information, coated in viral protein molecules, and surrounded by a lipid membrane. It is crucial that the viral RNA genome is packaged up into the viral particles, so it can carry the genetic information that the virus needs to infect new cells. The virion particles are very small, so other RNA molecules from the host cell need to be excluded. However, it is still unclear how these viruses know which RNA molecule it its own genome.
Some coronaviruses, including mouse coronavirus and human coronavirus OC43, encode a packaging signal: this RNA structure is recognized by the viral nucleocapsid protein and promotes incorporation of full-length genomes into assembling particles. We want to understand how this packaging signal works, whether other regions of the genome contribute to packaging, and how this process is achieved in other viruses.
RNA structure dynamics
RNA molecules can adopt many different shapes which can have different functions. RNA virus genomes can adopt different conformations to regulates stages of their lifecycles. We’re using RNA sequencing methods to investigate these structures (SHAPE-MaP, DMS-MaP-seq).