Phylogeography of infectious disease: genetic diversity and connectivity of the Ostreid herpesvirus 1 population in France

The genetic diversity of viral populations is a key to understanding ther phylogeographic and dissemination history of viruses, but studying the diversity of whole genomes from natural populations remains a challenge. Molecular ecology approaches are commonly used for RNA viruses harboring small genomes, but have only rarely been applied to DNA viruses with large genomes. Here, we used the Pacific oyster mortality syndrome (POMS, a disease that affects oyster farms around the world) as a model to study the genetic diversity of its causative agent, the Ostreid herpesvirus 1 (OsHV-1) in the three main French oyster-farming areas. Using ultra-deep sequencing on individual moribund oysters and new bioinformatics methodology, we de novo assembled 21 OsHV-1 genomes. Combining whole-genome comparisons with phylogenetic analysis and quantification of major and minor variants, we assessed the connectivity of OsHV-1 viral populations between the three oyster-farming areas. Our results suggest that the Marennes-Oleron Bay represents the main source of OsHV-1 diversity, from where the virus has dispersed to other farming areas, a scenario consistent with current practices of oyster transfers in France. Here, we demonstrate that molecular ecology approaches can be applied to large-genome viruses to determine the extent of their genetic diversity and better understand the spread of viral populations in natural environments