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

Delmotte, Jean; Pelletier, Camille; Morga, Benjamin; Galinier, Richard; Jacquot, Maude; Petton, Bruno; Lamy, Jean-Baptiste; Kaltz, Oliver; Avarre, Jean-Christophe; Montagnani, Caroline; Escoubas, Jean-Michel

The genetic diversity of viral populations is a key to understanding the spatial and temporal diffusion history of viruses, but studying the diversity of whole genomes from natural populations remains a challenge. Phylodynamic approaches are commonly used for RNA viruses harboring small genomes, but have only rarely been applied to DNA viruses with larger 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 new genomes. Combining quantification of major and minor variants, phylogenetic analysis and ancestral state reconstruction of discrete traits approaches; we assessed the connectivity of OsHV-1 viral populations between the three oyster-farming areas. Our results suggest that the Marennes-Oléron 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 phylodynamic approaches can be applied to marine DNA viruses to determine how epidemiological, immunological, and evolutionary processes act and potentially interact to shape their diversity patterns. Importance Phylogeography is a field of research that attempts to reconstruct the relationships between individual genotypes within a species and then correlate these genealogical relationships with their geographic and temporal origin. This field of research has become an essential step in the understanding of pandemics, in particular to determine the origin, spread and evolution of a pathogen as currently illustrated in studies on viral pandemics. However, because phylogeographic analyses are based on genome variation, stable genomes yield less information than labile genomes. Accordingly, viruses with double-stranded DNA (dsDNA) genomes generally have lower nucleotide diversity than RNA viruses. In this study, by combining the use of both major and minor variants with phylogeographic analyses of the oyster herpesvirus OsHV-1, we highlight genealogical relationships that have not been depicted in phylogenetic trees based on consensus viral genomes only. These data offer a plausible scenario reflecting the origin and spread of OsHV-1 populations between oyster-farming sites.