View source for Turtle fibropapillomatosis

{{Short description|Species of virus}}
{{Virusbox
| image         = Turtlewithfptumors0149026.jpg
| image_alt     = 
| image_caption = Hawaiian green turtle with severe fibropapilloma tumors. [[Wrasse#Cleaner wrasse|Cleaner wrasses]] avoid feeding on the tumours.
| parent        = Scutavirus
| species       = Chelonid alphaherpesvirus 5
| synonyms      = 
}}

'''Turtle fibropapillomatosis''' ('''FP''') is a disease of [[sea turtle]]s. The condition is characterized by benign but ultimately debilitating [[epithelium|epithelial]] tumours on the surface of biological tissues.<ref name="Sentinels">
{{cite journal | last1=Aguirre | first1=A. A. | last2=Lutz | first2=P.L. | title=Marine turtles as Sentinels of Ecosystem Health: Is fibropapillomatosis an indicator? | journal=Ecohealth | year=2004 | volume=1 | issue=3 | pages=275–283 | doi= 10.1007/s10393-004-0097-3| s2cid=42838117 }}</ref> FP exists all over the world, but it is most prominent in warmer climates, affecting up to 50–70% of some populations.<ref name="Sentinels" />

The causative agent of the disease is believed to be '''''Chelonid alphaherpesvirus 5''''' (ChHV-5), a species of virus in the genus ''[[Scutavirus]]'', subfamily ''[[Alphaherpesvirinae]]'', family ''[[Herpesviridae]]'', and order ''[[Herpesvirales]]''.<ref>{{Cite journal|last=Morrison CL, Iwanowicz L, Work TM, Fahsbender E, Breitbart M, Adams C, Iwanowicz D, Sanders L, Ackermann M, Cornman RS|date=2018|title=Genomic evolution, recombination, and inter-strain diversity of chelonid alphaherpesvirus 5 from Florida and Hawaii green sea turtles with fibropapillomatosis.|journal=PeerJ|volume=6|pages=e4386|doi=10.7717/peerj.4386|pmid=29479497|pmc=5824677 |doi-access=free }}</ref><ref>{{Cite web|url=https://talk.ictvonline.org/files/master-species-lists/m/msl/8266|title=ICTV Master Species List 2018b.v2|website=International Committee on Taxonomy of Viruses (ICTV)|access-date=19 June 2019}}{{dead link|date=January 2023|bot=medic}}{{cbignore|bot=medic}}</ref><ref name="FPTHV">
{{cite journal | last1=Ackermann | first1=M. | last2=Koriabine | first2=M. | last3=Hartmann-Fritsch | first3=F. | last4=de jong | first4=P. J. | last5=Lewis | first5=T. D. | title=The Genome of Chelonid Herpesvirus 5 Harbours Atypical Genes | journal=PLOS ONE | year=2012 | volume=7 | issue=10 | pages=e46623 | doi=10.1371/journal.pone.0046623| pmid=23056373 | pmc=3462797 |display-authors=etal| bibcode=2012PLoSO...746623A | doi-access=free }}</ref> [[Turtle leech]]es are suspected mechanical [[Vector (epidemiology)|vectors]], transmitting the disease to other individuals.<ref name="Ozobranchus">
{{cite journal | last1=Greenblatt | first1=R. J. | last2=Work | first2=T. M. | last3=Balazs | first3=G. H. | last4=Sutton | first4=C. A. | last5=Casey | first5=R. N. | title=The Ozobranchus leech is a candidate mechanical vector for the fibropapilloma-associated turtle herpesvirus found latently infecting skin tumors on Hawaiian green turtles (''Chelonia mydas'') | journal=Virology | year=2004 | volume=321 | issue=1 | pages=101–110 | doi=10.1016/j.virol.2003.12.026|display-authors=etal | pmid=15033569| doi-access=free }}</ref> The disease is thought to have a multifactorial cause, including a tumour-promoting phase that is possibly caused by [[Toxin#biotoxins|biotoxins]] or contaminants.<ref name="Lyngbyamajuscula">
{{cite journal | last1=Arthur | first1=K. | last2=Limpus | first2=C. | last3=Balazs | first3=G. H. | last4=Capper | first4=A. | last5=Udy | first5=J. | title=The Exposure of Green Turtles (''Chelonia mydas'') to Tumour Promoting Compounds Produced by the Cyanobacterium ''Lyngbya majuscula'' and their Potential Role in the Aetiology of Fibropapillomatosis | journal=Harmful Algae | year=2008 | volume=7 | issue=1 | pages=114–125 | doi=10.1016/j.hal.2007.06.001| bibcode=2008HAlga...7..114A |display-authors=etal}}</ref>

==Description==

[[File:Green turtle with fibropapillomatosis.jpg|thumb|right|A green sea turtle with significant fibropapilloma tumours basking on a beach north of [[Haleiwa, HI]]]]
Fibropapillomatosis  is a benign tumour disease of marine turtles, predominantly in the [[green sea turtle]], ''Chelonia mydas'', but it has also been reported in the [[loggerhead sea turtle]] ''Caretta caretta'', [[olive ridley sea turtle|olive ridley]] ''Lepidochelys olivacea'', [[Kemp's ridley sea turtle|Kemp's ridley]] ''Lepidochelys kempii'', and [[leatherbacks]] ''Dermochelys coriacea''.<ref name="Sentinels" /> This [[neoplastic disease]] causes proliferation of papillary cells ([[hyperplasia]]) and gives rise to excess fibrous connective tissue in both epidermal and dermal skin layers – or more specifically, proliferation of dermal fibroblasts and epidermal keratinocytes.<ref name="Bovine">
{{cite journal  | last1=Tan | first1=M. T. | last2=Yildirim | first2=Y. | last3=Sozmen | first3=M. | last4=Bilge-Dagalp | first4=S. | last5=Yilmaz | first5=V. | title=A Histopathological, Immunohistochemical and Molecular Study of Cutaneous Bovine Papillomatosis | journal=Kafkas Univ Vet Fak Derg | year=2012 | volume=18 | issue=5 | pages=739–744 | doi=10.9775/kvfd.2012.5341| doi-broken-date=1 November 2024 |display-authors=etal| doi-access= }}</ref><ref name="ImmuneStatus">{{cite journal | last1=Work | first1=T. M. | last2=Rameyer | first2=R. A. | last3=Balazs | first3=G. H. | last4=Cray | first4=C. | last5=Chang | first5=S. P. | title=Immune status of free ranging green turtles with fibropapillomatosis from Hawaii | journal=Journal of Wildlife Diseases | year=2001 | volume=37 | issue=3 | pages=574–581 | doi=10.7589/0090-3558-37.3.574 | pmid=11504232 | s2cid=14386579 | doi-access=free }}</ref> This causes [[tumorigenesis]] in sizes less than 1&nbsp;cm up to more than 30&nbsp;cm in diameter.<ref name="Sentinels" />
FP is most often found externally around the armpits, genitals, neck, eyes, and tails of turtles, but  also occur in and around the mouth, and rarely in internal organs or on the carapace. This, in turn, impedes vision, feeding, and movement.<ref name="Sentinels" /> Around 25–30% of turtles with external tumours also have internal tumours, primarily in heart, lungs and kidneys.<ref name="Sentinels" />

FP incidence is highest among immature and juvenile green turtles, while it is rare in adults.<ref name="ImmuneStatus" /> The suggestions for this pattern include the tumours can regress and be cured, which has been documented in some individuals, even when tumours were severe.<ref name="Stranded">
{{cite journal  | last1=Foley | first1=A. M. | last2=Schroeder | first2=B. A. | last3=Redlow | first3=A. E. | last4=Fick-Child | first4=K. J. | last5=Teas | first5=W. G. | title=Fibropapillomatosis in Stranded Green Turtles (Chelonia mydas) from the Eastern United States (1980–98): Trends and Associations with Environmental factors | journal=Journal of Wildlife Diseases  | year=2005 | volume=41 | issue=1 | pages=29–41 | doi=10.7589/0090-3558-41.1.29 | pmid=15827208 | doi-access=free }}</ref> However, the responses that cause these tumour regressions is unknown. Secondly, the juvenile individuals with FP [[survivorship bias|might die before reaching adulthood]].<ref name="Stranded" />

===Prognosis===

The tumours appear to be benign and can be present for many years, but if large, can mechanically hamper sight, swallowing, and swimming, which may ultimately be fatal.<ref name="Sentinels" /> While external tumours hamper movement and sight, internal tumours interfere with system functioning, another potentially fatal factor.<ref name="Sentinels" /> As the tumours progress, individuals with large numbers of tumours may become [[anaemic]], have a lack of proteins and iron, and in more advanced stages even suffer from [[acidosis]] caused by imbalanced calcium/phosphorus ratios and severe [[emaciation]].<ref name="Sentinels" />

===Other species===
Fibropapillomas are present in other animal groups, but are caused by different viruses, for example the [[bovine papillomavirus]].<ref name="Bovine" />

==History==
The first documented case of the disease was in 1938 in Key West, Florida.<ref name="Sentinels" /> Long-term studies found no signs of the disease on Florida's Atlantic coast in the 1970s, but during the 1980s FP was recorded in incidences varying from 28 to 67%.<ref name="Sentinels" /> Today, incidences as high as 92% have been reported in Kaneohe Bay, Oahu, Hawaii. Generally, FP is most prominent in warmer climates. Recent research has found that FP is caused by stress and tumours have been observed in turtles that are part of turtle tourism tours. <ref name="Sentinels" />

==Cause==
<!-- Deleted image removed: [[File:Ozobranchus margoi.jpg|thumb|left|The turtle leech species ''Ozobranchus margoi'' is one of the suspected mechanical vectors of the herpesvirus that causes fibropapillomatosis]] -->
The FP is an infectious disease with [[horizontal transmission]].<ref name="Sentinels" /> An [[Alphaherpesvirinae|alphaherpesvirus]] initially called fibropapilloma-associated turtle herpesvirus (FPTHV), and now called ''Chelonid alphaherpesvirus 5'', is believed to be the causative agent of the disease. The reason for this belief is because nearly all tissue samples tested from turtles with lesions carry genetic material of this herpesvirus, varying between 95 and 100% depending on different studies and locations.<ref name="Sentinels" /><ref name="FPTHV" /><ref name="Lyngbyamajuscula" /> The DNA loads of the herpesvirus in tumour tissue are 2.5–4.5 logarithms higher than in uninfected tissue.<ref name="Sequences">
{{cite journal | last1=Quackenbush | first1=S. L. | last2=Casey | first2=R. N. | last3=Murcek | first3=R. J. | last4=Paul | first4=T. A. | last5=Work | first5=T. M.  |display-authors=etal | title=Quantitative Analysis of Herpesvirus Sequences from Normal Tissue and Fibropapillomas of Marine Turtles with Real-Time PCR | journal=Virology | year=2001 | volume=287 | issue=1 | pages=105–111 | doi=10.1006/viro.2001.1023 | pmid=11504546| doi-access=free }}</ref>
The FPTHV herpesvirus has been found in turtles free from FP and this suggest that the FP progression is multifactorial and might even involve some sort of tumour-promoting phase.<ref name="Lyngbyamajuscula" /> The global prevalence of the disease also suggests a multifactorial cause, rather than single factors or agents.<ref name="Lyngbyamajuscula" /><ref name="Challenges">
{{cite journal | last1=Herbst | first1=L. H. | last2=Klein | first2=P. A. | title=Green Turtle Fibropapillomatosis: Challenges to Assessing the Role of Environmental Cofactors | journal=Environmental Health Perspectives | year=1995 | volume=103 | issue=4 | pages=27–30 | pmc=1519284 | pmid=7556020 | doi=10.2307/3432408| jstor=3432408 }}</ref> Possible factors include some parasites, bacteria, environmental pollutants, UV-light, changing water temperatures and biotoxins. Even physiological factors such as stress and immunologic status appear to be associated with FP.<ref name="Sentinels" />

The leech genus ''[[Ozobranchus]]'' is thought to be the mechanical vector of the herpesvirus, transmitting the virus from one turtle to another. These leeches are common turtle [[Parasitism#Types|ectoparasites]] that exclusively feed on turtle blood, and some leeches have been found carrying more than 10 million copies of the herpesvirus DNA.<ref name="Ozobranchus" /> 
The green sea turtle is an herbivore and feeds primarily on seagrass and macroalgae.<ref name="Lyngbyamajuscula" /><ref name="ImmuneStatus" /> Two toxins which are suspected to be associated with FP are found epiphytically on these plants.<ref name="Sentinels" /><ref name="Lyngbyamajuscula" /> First, the toxic compound [[lyngbyatoxin]] from the cyanobacterium Lyngbya majuscule,<ref name="Lyngbyamajuscula" /> and second the toxin [[okadaic acid]] – a documented tumour-promoting toxin - from the dinoflagellate  ''[[Prorocentrum]]''.<ref name="Sentinels" /> Again, causality has not been concluded, but an association seems to exist between the distribution of especially the dinoflagellates and the occurrence of FP, and as they are found on weeds, they can be ingested by foraging green sea turtles.<ref name="Sentinels" /><ref name="Lyngbyamajuscula" />
Turtles with FP are found to have a compromised immune system.<ref name="ImmuneStatus" /> They have higher phagocytic leucocyte counts (especially [[heterophil]]s) compared to healthy individuals, which seems to be an effect of FP, as it is mostly evident in individuals with severe tumours.<ref name="ImmuneStatus" /><ref name="Associations">
{{cite report | last1=Lutz | first1=P. L. | last2=Cray | first2=C. | last3=Sposato | first3=P. L. | title=Studies of the association between immunosuppression and fibropapillomatosis within three habitats of ''Chelonia mydas'' | publisher=Southwest Fisheries Science Center | date=2001 | url=http://www.pifsc.noaa.gov/library/pubs/admin/SWFC_Admin_Report_01-01C.pdf}}</ref> This further supports the hypothesis of the herpesvirus as a causative agent.<ref name="Associations" /> Immunosuppression is strongly correlated with FP, but does seem to be a consequence of the development and growth of FP rather than a prerequisite, which is similar to other virus-induced tumour diseases in other species, such as  Marek's disease in poultry.<ref name="Sentinels" /><ref name="ImmuneStatus" />

== Treatment ==
Surgical removal of tumors caused by FP is the most common treatment method. [[Photodynamic therapy]] and [[electrochemotherapy]] are also used,<ref>{{Cite web|url=https://www.cabi.org/isc/datasheet/82638|title=fibropapillomatosis of sea turtles|website=www.cabi.org|access-date=2018-08-13}}</ref> as is CO<sub>2</sub> laser surgery.<ref>{{cite journal |last1=Page-Karjian |first1=A |last2=Norton |first2=TM |last3=Krimer |first3=P |last4=Groner |first4=M |last5=Nelson SE |first5=Jr |last6=Gottdenker |first6=NL |title=Factors influencing survivorship of rehabilitating green sea turtles (Chelonia mydas) with fibropapillomatosis. |journal=Journal of Zoo and Wildlife Medicine |date=September 2014 |volume=45 |issue=3 |pages=507–19 |doi=10.1638/2013-0132R1.1 |pmid=25314817|s2cid=8090102 }}</ref>

==Epidemiology==

FP affects green sea turtle populations all over the world, making it a [[panzootic]].<ref name="Sentinels" /> It is especially found in warmer climates, such as the Caribbean, Hawaii, Japan, and Australia, where up to 70% of individuals in a population have FP.<ref name="Sentinels" />

Epidemiological links are seen between FP rates, nitrogen footprints, and invasive macroalgae.<ref name="Macroalgae">
{{cite journal | last1=Van Houtan | first1=K. S. | last2=Hargrove | first2=S. K. | last3=Balazs | first3=G. H. | title=Land Use, Macroalgae and a Tumour-Forming Disease in Marine Turtles | journal= PLOS ONE | year=2010 | volume=5 | issue=9 | pages=e12900 | doi=10.1371/journal.pone.0012900 | pmid=20927370 | pmc=2947502 | bibcode=2010PLoSO...512900V | doi-access=free }}</ref> The strongest association with FP is with habitat type, especially increased anthropogenic activity causing high-nitrogen footprints in a surrounding environment where green sea turtles are found.<ref name="Lyngbyamajuscula" /><ref name="ImmuneStatus" /><ref name="Macroalgae" /> Sea turtles do live in very complex ecosystems, with both near-shore habitats and several years in the open ocean, which makes  study of ecosystem associations difficult.<ref name="ImmuneStatus" /> Even so, observations support the hypothesis that near-shore habitats have a strong correlation with the disease, as newly recruited individuals from the pelagic life phase have never been found with tumours,<ref name="Lyngbyamajuscula" /> and when migrating to more shallow ocean zones, such as the [[neritic zone]], individuals still remain free from FP, but when entering lagoon systems, turtles may become infected.<ref name="Macroalgae" /> The high prevalence of FP is also associated with habitats’ poor quality, while FP is absent in some habitats of good quality.<ref name="Macroalgae" />

Turtles are known to be robust to physical damage, but are surprisingly very susceptible to biological and chemical contaminants caused by anthropogenic activity.<ref name="Macroalgae" /> As the turtles forage on invasive macroalgae in nutrient-rich waters, they can ingest environmental nitrogen in the form of arginine, which is known to regulate immune activity, promote herpesviruses, and contribute to tumorigenesis.<ref name="Macroalgae" />

==References==
{{Reflist}}

==External links==
* {{Wikispecies-inline|Chelonid alphaherpesvirus 5|''Chelonid alphaherpesvirus 5''}}
* Observations on [https://www.inaturalist.org/taxa/968116-Chelonid-alphaherpesvirus-five iNaturalist]
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{{Herpesvirales}}
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[[Category:Sea turtles]]
[[Category:Turtle terminology]]