Insights into parvovirus packaging through structural characterization of DNA-capsid interactions
The Kaelber lab uses cryoEM to understand the structure-phenotype relationships of viruses, including parvoviruses used in gene therapy. Parvoviral vectors are limited in their DNA packaging capacity, so we contrasted the structures of adeno-associated virus containing different amounts of DNA to see how the capsid changes on filling. For adeno-associated virus, we find that DNA does not bind in the nucleotide-binding pocket on the capsid interior until the virion is almost fully stuffed. As the virus hits its maximum capacity, genomic nucleotides base-stack around an exposed proline ring.
To crack a nationwide pandemic in farmed beetles, we used cryoEM to directly identify the previously-unknown causative virus without genome sequencing. This parvovirus has unprecedented genomic ssDNA ordering, with ~12% of the DNA ordered in the structure by capsid-binding (and suggests design strategies for engineering of increased AAV packaging). We confirmed etiological association by in vivo experiments. The diagnostic workflow provides proof-of-concept that could be applied to outbreaks in humans or other species.
Hosted by Professor Lu Wang
~Coffee/tea will be served prior to the lecture~