Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors

Sea turtle populations are under threat from an epizootic tumor disease (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at many longer-affected sites globally. However, we do not yet understand the precise environmental, mutational and viral events driving fibropapillomatosis tumor formation and progression. Here we perform transcriptomic and immunohistochemical profiling of five fibropapillomatosis tumor types: external new, established and postsurgical regrowth tumors, and internal lung and kidney tumors. We reveal that internal tumors are molecularly distinct from the more common external tumors. However, they have a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. These conserved oncogenic drivers recapitulate remarkably well the core pan-cancer drivers responsible for human cancers. Fibropapillomatosis has been considered benign, but metastatic-related transcriptional signatures are strongly activated in kidney and established external tumors. Tumors in turtles with poor outcomes (died/euthanized) have genes associated with apoptosis and immune function suppressed, with these genes providing putative predictive biomarkers. Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, inter-tumor relationships, and therapeutic treatment for this wildlife epizootic

Evolutionary comparisons of chelonid alphaherpesvirus 5 (ChHV5) genomes from fibropapillomatosis-afflicted green (chelonia mydas), Ooive ridley (lepidochelys olivacea) and kemp’s ridley (lepidochelys kempii) sea turtles

peer-reviewedThe 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 viru

Plastic ingestion in post-hatchling sea turtles: assessing a major threat in Florida near shore waters

Pollution from anthropogenic marine debris, particularly buoyant plastics, is ubiquitous across marine ecosystems. Due to the persistent nature of plastics in the environment, their buoyancy characteristics, degradation dynamics, and ability to mimic the behavior of natural prey, there exists significant opportunity for marine organisms to ingest these man-made materials. In this study we examined gastrointestinal (GI) tracts of 42 post-hatchling loggerhead (Caretta caretta) sea turtles stranded in Northeast Florida. Necropsies revealed abundant numbers of plastic fragments ranging from 0.36 to 12.39 mm in size (length), recovered from the GI tracts of 39 of the 42 animals (92.86%), with GI burdens ranging from 0 to 287 fragments with a mass of up to 0.33 g per turtle. Post-hatchlings weighed from 16.0 to 47.59 g yielding a plastic to body weight percentage of up to 1.23%. Several types of plastic fragments were isolated, but hard fragments and sheet plastic were the most common type, while the dominant frequency of fragment color was white. Fragment size and abundance mixed with natural gut contents suggests significant negative health consequences from ingestion in animals at this life stage. Gaining greater insight into the prevalence of plastic ingestion, the types of plastic and the physiological effects of plastic consumption by multiple life-stages of sea turtles will aid the prioritization of mitigation efforts for the growing marine debris problem. This report demonstrates that plastic ingestion is a critical issue for marine turtles from the earliest stages of life

Environmental DNA monitoring of oncogenic viral shedding and genomic profiling of sea turtle fibropapillomatosis reveals unusual viral dynamics

Pathogen-induced cancers account for 15% of human tumors and are a growing concern for endangered wildlife. Fibropapillomatosis is an expanding virally and environmentally coinduced sea turtle tumor epizootic. Chelonid herpesvirus 5 (ChHV5) is implicated as a causative virus, but its transmission method and specific role in oncogenesis and progression is unclear. We applied environmental (e)DNA-based viral monitoring to assess viral shedding as a direct means of transmission, and the relationship between tumor burden, surgical resection and ChHV5 shedding. To elucidate the abundance and transcriptional status of ChHV5 across early, established, regrowth and internal tumors we conducted genomics and transcriptomics. We determined that ChHV5 is shed into the water column, representing a likely transmission route, and revealed novel temporal shedding dynamics and tumor burden correlations. ChHV5 was more abundant in the water column than in marine leeches. We also revealed that ChHV5 is latent in fibropapillomatosis, including early stage, regrowth and internal tumors; higher viral transcription is not indicative of poor patient outcome, and high ChHV5 loads predominantly arise from latent virus. These results expand our knowledge of the cellular and shedding dynamics of ChHV5 and can provide insights into temporal transmission dynamics and viral oncogenesis not readily investigable in tumors of terrestrial species

Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors

Sea turtle populations are under threat from an epizootic tumor disease (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at many longer-affected sites globally. However, we do not yet understand the precise environmental, mutational and viral events driving fibropapillomatosis tumor formation and progression. Here we perform transcriptomic and immunohistochemical profiling of five fibropapillomatosis tumor types: external new, established and postsurgical regrowth tumors, and internal lung and kidney tumors. We reveal that internal tumors are molecularly distinct from the more common external tumors. However, they have a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. These conserved oncogenic drivers recapitulate remarkably well the core pan-cancer drivers responsible for human cancers. Fibropapillomatosis has been considered benign, but metastatic-related transcriptional signatures are strongly activated in kidney and established external tumors. Tumors in turtles with poor outcomes (died/euthanized) have genes associated with apoptosis and immune function suppressed, with these genes providing putative predictive biomarkers. Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, inter-tumor relationships, and therapeutic treatment for this wildlife epizootic