Comparative Pathology and Pathogenesis of Spontaneous and Experimentally Induced Fibropapillomas of Green Turtles (<i>Chelonia mydas</i>)

Herbst, Lawrence H.; Jacobson, Eric S.; Klein, Paul; Balazs, George H.; Moretti, Ritchie H.; Brown, Timothy; Sundberg, John P.

doi:10.1354/vp.36-6-551

Cited by 101 publications

(105 citation statements)

References 45 publications

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“…Keratins may also inhibit migration of inflammatory cells to the epidermis, thus shielding viruses from the host immune response (54). Supporting this conjecture is the pathology of epidermal fibropapillomas in green turtles, in which dermal lymphoid infiltrates are common but epidermal inflammation is rare (55). Thus, maturing KC may offer the only refugia where the virus can carry out the entire lytic phase of reproduction and may protect the virus when skin cells are shed, thereby facilitating transmission.…”

Section: Discussionmentioning

confidence: 99%

In VitroReplication of Chelonid Herpesvirus 5 in Organotypic Skin Cultures from Hawaiian Green Turtles (Chelonia mydas)

Work

Dagenais

Weatherby

et al. 2017

J Virol

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Fibropapillomatosis (FP) is a tumor disease of marine turtles associated with chelonid herpesvirus 5 (ChHV5), which has historically been refractory to growth in tissue culture. Here we show, for the first time, de novo formation of ChHV5-positive intranuclear inclusions in cultured green turtle cells, which is indicative of active lytic replication of the virus. The minimal requirements to achieve lytic replication in cultured cells included (i) either in vitro cultures of ChHV5-positive tumor biopsy specimens (plugs) or organotypic cultures (rafts) consisting of ChHV5-positive turtle fibroblasts in collagen rafts seeded with turtle keratinocytes and (ii) keratinocyte maturation induced by raising raft or biopsy cultures to the air-liquid interface. Virus growth was confirmed by detailed electron microscopic studies that revealed intranuclear sun-shaped capsid factories, tubules, various stages of capsid formation, nuclear export by budding into the perinuclear space, tegument formation, and envelopment to complete de novo virus production. Membrane synthesis was also observed as a sign of active viral replication. Interestingly, cytoplasmic particles became associated with keratin filaments, a feature not seen in conventional monolayer cell cultures, in which most studies of herpesvirus replication have been performed. Our findings draw a rich and realistic picture of ChHV5 replication in cells derived from its natural host and may be crucial not only to better understand ChHV5 circulation but also to eventually complete Koch's postulates for FP. Moreover, the principles described here may serve as a model for culture of other viruses that are resistant to replication in conventional cell culture.IMPORTANCE A major challenge in virology is the study of viruses that cannot be grown in the laboratory. One example is chelonid herpesvirus 5 (ChHV5), which is associated with fibropapillomatosis, a globally distributed, debilitating, and fatal tumor disease of endangered marine turtles. Pathological examination shows that ChHV5 is shed in skin. Here we show that ChHV5 will grow in vitro if we replicate the complex three-dimensional structure of turtle skin. Moreover, lytic virus growth requires a close interplay between fibroblasts and keratinocytes. Finally, the morphogenesis of herpesviral growth in three-dimensional cultures reveals a far richer, and likely more realistic, array of capsid morphologies than that encountered in traditional monolayer cell cultures. Our findings have applications to other viruses, including those of humans.KEYWORDS herpesvirus, electron microscopy, immunohistochemistry, morphogenesis, pathobiology

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Section: Discussionmentioning

confidence: 99%

In VitroReplication of Chelonid Herpesvirus 5 in Organotypic Skin Cultures from Hawaiian Green Turtles (Chelonia mydas)

Work

Dagenais

Weatherby

et al. 2017

J Virol

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“…Green turtle fibropapillomatosis (GTFP) is characterized by multiple cutaneous papillomas, fibromas, and fibropapillomas, as well as occasional visceral fibromas (Herbst et al 1999). To our knowledge, our study constitutes the first description of squamous cell carcinoma in sea turtles.…”

Section: Discussionmentioning

confidence: 99%

Metastatic squamous cell carcinoma in two loggerhead sea turtles Caretta caretta

Orós

Tucker²,

Fernández³

et al. 2004

Dis. Aquat. Org.

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We received 2 stranded loggerhead sea turtles (Caretta caretta) with squamous cell carcinomas to necropsy. The dead turtles had been collected in Gran Canaria and Fuerteventura in April 1994 and May 1997, respectively to determine the cause of death. One turtle had 3 ulcerated lesions in the dorsal part of the neck and several irregular masses in the lungs and kidneys. Histologic examination of lesions in the skin, lungs, kidneys, and ventricular myocardium revealed neoplastic proliferation of abnormal keratinocytes. Ultrastructural examination identified the tumoral cells as epithelial cells. The second turtle had 4 lesions in the skin of the head and flippers, and several irregular masses in the lungs, liver, and kidneys. Histological examination revealed a squamous cell carcinoma with metastases to muscle tissue, liver, lungs, and kidneys. Attempts to characterize the tumoral cells by immunohistochemistry using several monoclonal and polyclonal antisera against high and low molecular weight cytokeratins from mammals, as well as vimentin and desmin, failed. Differences between reptilian keratins (mainly β-keratins) and mammalian keratins (mainly α-keratins) could explain this absence of immunoreactivity. This is the first description of squamous cell carcinoma in sea turtles. KEY WORDS: Squamous cell carcinoma · Loggerhead turtle · Caretta caretta · Sea turtle · Reptile · Immunohistochemistry Resale or republication not permitted without written consent of the publisherDis Aquat Org 58: [245][246][247][248][249][250] 2004 of 20 to 30 turtles per year. We report here the histopathological features of 2 cases of metastasizing squamous cell carcinoma in the loggerhead sea turtle Caretta caretta. MATERIALS AND METHODSWithin a 3 yr period (i.e. in April 1994 and May 1997), 2 stranded loggerhead sea turtles with squamous cell carcinomas were submitted to the Veterinary Faculty, ULPGC. The first was a 6.5 kg juvenile female stranded in Gran Canaria (27°40' N, 15°20' W). The turtle had a curved carapace length and width of 33 and 31 cm respectively, and a straight carapace length and width of 29 and 28 cm respectively. After stranding, the turtle had been housed in an aquarium at the Wildlife Rehabilitation Center of Tafira, Gran Canaria. Physical examination had revealed anorexia and lethargy. Despite forcefeeding and intramuscular administration of antimicrobial enrofloxacin, the turtle died 1 wk after stranding. The second turtle was a 7.2 kg juvenile female found stranded dead in Fuerteventura (28°10' N, 14°20' W). This turtle had a curved carapace length and width of 34 and 33 cm respectively, and a straight carapace length and width of 31 and of 30 cm respectively.The gross postmortem examinations of both turtles were carried out using the protocol developed by Wolke & George (1981). Fecal specimens were processed following techniques described by Boch & Supperer (1982).Macroscopic lesions were recorded and tissue samples from all major organs were fixed in 10% neutral buffered formalin, embedded i...

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“…The possibility of genetic resistance to FP suggests that rehabilitation of FP-afflicted turtles may be inappropriate, as such activities may maintain a greater level of individuals that are genetically susceptible to FP in the population, and thus alter the natural auto-limitation of the disease within the larger green turtle population. The tumor-excised turtles also continue carrying the latent herpesvirus and potentially transmit it to others (Herbst et al 1999).…”

Section: Characterization Of Fp Occurrencementioning

confidence: 99%

Health condition of juvenile Chelonia mydas related to fibropapillomatosis in southeast Brazil

Santos¹,

Martins²,

Baptistotte³

et al. 2015

Dis. Aquat. Org.

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Packed cell volume (PCV), plasma biochemistry, visual body condition (BC), and calculated body condition index (BCI) were evaluated in 170 wild juvenile green sea turtles Chelonia mydas from an aggregation in the effluent canal of a steel mill in Brazil. Occurrence of cutaneous fibropapillomatosis (FP) was observed in 44.1% of the animals examined. BCI alone did not differ significantly between healthy animals and those afflicted with FP. However, all turtles with low BCI were severely afflicted and were uremic, hypoglycemic, and anemic in relation to healthy animals. Severe FP was not always reflected by a poor health condition of the individual. Clinical evaluation and plasma biochemistry indicated that most animals afflicted with FP were in good health condition. Differences in FP manifestations and associated health conditions in different geographic regions must be assessed by long-term health monitoring programs to help define priorities for conservation efforts.

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Comparative Pathology and Pathogenesis of Spontaneous and Experimentally Induced Fibropapillomas of Green Turtles (Chelonia mydas)

Cited by 101 publications

References 45 publications

In VitroReplication of Chelonid Herpesvirus 5 in Organotypic Skin Cultures from Hawaiian Green Turtles (Chelonia mydas)

In VitroReplication of Chelonid Herpesvirus 5 in Organotypic Skin Cultures from Hawaiian Green Turtles (Chelonia mydas)

Metastatic squamous cell carcinoma in two loggerhead sea turtles Caretta caretta

Health condition of juvenile Chelonia mydas related to fibropapillomatosis in southeast Brazil

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