Evolutionary Comparisons of Chelonid Alphaherpesvirus 5 (ChHV5) Genomes from Fibropapillomatosis-Afflicted Green (Chelonia mydas), Olive Ridley (Lepidochelys olivacea) and Kemp’s Ridley (Lepidochelys kempii) Sea Turtles

The spreading global sea turtle fibropapillomatosis (FP) epizootic is threatening some of
Earth’s ancient reptiles, adding to the plethora of threats faced by these keystone species. Understanding
this neoplastic disease and its likely aetiological pathogen, chelonid alphaherpesvirus 5
(ChHV5), is crucial to understand how the disease impacts sea turtle populations and species and
the future trajectory of disease incidence. We generated 20 ChHV5 genomes, from three sea turtle
species, to better understand the viral variant diversity and gene evolution of this oncogenic virus.
We revealed previously underappreciated genetic diversity within this virus (with an average of
2035 single nucleotide polymorphisms (SNPs), 1.54% of the ChHV5 genome) and identified genes
under the strongest evolutionary pressure. Furthermore, we investigated the phylogeny of ChHV5 at
both genome and gene level, confirming the propensity of the virus to be interspecific, with related
variants able to infect multiple sea turtle species. Finally, we revealed unexpected intra-host diversity, with up to 0.15% of the viral genome varying between ChHV5 genomes isolated from different
tumours concurrently arising within the same individual. These findings offer important insights
into ChHV5 biology and provide genomic resources for this oncogenic virus.