A Comparison of Parapoxviruses in North American Pinnipeds
Abstract
Parapoxviruses cause nodular lesions on the skin and mucosal membranes of pinnipeds and infections by these viruses have been documented worldwide. Seal parapoxvirus is currently classified as a tentative species of the Parapoxvirus genus. Tissue or swab samples were analyzed from 11 pinnipeds of different host species undergoing rehabilitation on the east and west coasts of the United States of America (USA) that were positive for parapoxvirus. The aim of the study was to compare parapoxvirus sequences of fragments of the B2L, DNA polymerase, GIF and viral interleukin-10 ortholog (vIL-10) genes and to examine the evolutionary relationship between viruses detected in different pinniped species and at different locations with other members of the Parapoxvirus genus, such as Orf virus (ORFV), Bovine papular stomatitis virus (BPSV) and Pseudocowpox virus (PCPV). The sequence analysis showed that the parapoxvirus sequences from the pinnipeds differed significantly from those found in terrestrial hosts and that they formed a separate cluster within the genus. Our results suggest that transmission of the same parapoxvirus strain is possible between different species, including between members of different families (phocids and otariids). Animals belonging to the same species but living in distant geographic locations presented genetically distant parapoxviruses. The findings of this study demonstrate that sealpox lesions in pinnipeds of different species are caused by viruses that belong to the Parapoxvirus genus but have significant genetic differences compared to the established virus species in terrestrial hosts, thus strongly supporting the classification of pinniped parapoxvirus as a new species of the genus.
Acknowledgments
We would like to thank: SeaWorld Parks and Entertainment's contribution (Technical Contribution number 2020-26); Prof. Dr. Ana Duarte from FMV-ULisboa; the animal care and laboratory staff and the volunteers at TMMC and especially acknowledge B. Halaska for shipping samples.
Footnotes
Funding. The publication charges for this article have been funded by an open access grant from the publication fund of UiT The Arctic University of Norway. The work was supported in part by NOAA Fisheries Service through a John H. Prescott Marine Mammal Rescue Assistance Grant to the One Health Institute and Karen C. Drayer Wildlife Health Center, UC Davis, Davis.
References
- 1. Hastings BE, Lowenstine LJ, Gage LJ, Munn RJ. An epizootic of seal pox in pinnipeds at a rehabilitation center. J Zoo Wild Med. (1989) 20:282–90. [PubMed]
- 2. Hicks BD, Worthy GJ. Sealpox in captive grey seals (Halichoerus grypus) and their handlers. J Wild Dis. (1987) 231:1–6. 10.7589/0090-3558-23.1.1 [] [[PubMed]
- 3. Müller G, Gröters S, Siebert U, Rosenberger T, Driver J, König M, et al. . Parapoxvirus infection in harbor seals (Phoca vitulina) from the German North Sea. Vet Pathol. (2003) 40:445–54. 10.1354/vp.40-4-445 [] [[PubMed]
- 4. Nollens HH, Jacobson ER, Gulland FMD, Beusse DO, Bossart GD, Hernandez JA, et al. . Pathology and preliminary characterization of a parapoxvirus isolated from a California Sea Lion (Zalophus Californianus). J Wild Dis. (2006) 42:23–32. 10.7589/0090-3558-42.1.23 [] [[PubMed]
- 5. Okada K, Fujimoto Y. The fine structure of cytoplasmic and intranuclear inclusions of seal pox. Jpn J Vet Sci. (1984) 46:401–4. 10.1292/jvms1939.46.401 [] [[PubMed]
- 6. Osterhaus AD, Broeders HW, Visser IK, Teppema JS, Kuiken T. Isolation of a parapoxvirus from pox-like lesions in grey seals. Vet Rec. (1994) 135:601–2. [[PubMed]
- 7. Wilson TM, Cheville NF, Karstad L. Seal pox. Wildlife Dis Assoc Bull. (1969) 5:412–8. 10.7589/0090-3558-5.4.412 [] [[PubMed]
- 8. Wilson TM, Cheville NF, Boothe AD. Sealpox questionnaire survey. J Wild Dis. (1972) 8:155–7. 10.7589/0090-3558-8.2.155 [] [[PubMed]
- 9. Hadlow WJ, Cheville NF LJW. Occurrence of pox in a northern fur seal on the Pribilof Islands in 1951. J Wild Dis. (1980) 16:305–12. 10.7589/0090-3558-16.2.305 [] [[PubMed]
- 10. Tryland M, Klein J, Nordøy ES, Blix AS. Isolation and partial characterization of a parapoxvirus isolated from a skin lesion of a Weddell seal. Virus Res. (2005) 108:83–7. 10.1016/j.virusres.2004.08.005 [] [[PubMed]
- 11. Wilson TM. Seal pox in a free living Harbor seal (Phoca vitulina). In: Annual Proceedings of American Association Zoo Veterinarians (1970). p. 125-7. [PubMed]
- 12. Wilson TM, Poglayen-Neuwall I. Pox in South American sea lions (Otaria byronia). Can J Comp Med. (1971) 35:174–7.
- 13. International Committee on Virus Taxonomy [ICTV] . Virus Taxonomy: 2018 Release. (2018). Available online at: (accessed February 25, 2019).
- 14. Moss B. Poxviridae. In Knipe DM, Howley PM. editors. Fields Virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; (2013). p. 2129–84. [PubMed]
- 15. Airas N, Hautaniemi M, Syrjä P, Knuuttila A, Putkuri N, Coulter L, et al. . Infection with possible novel parapoxvirus in horse, Finland, 2013. Emerg Infect Dis. (2016) 22:1242–45. 10.3201/eid2207.151636 ] [
- 16. Tryland M. Molecular Detection of Human Viral Pathogens. Oxfordshire: Taylor and Francis Group. (2011) p. 1029–37. [PubMed]
- 17. Duignan PJ, Van Bressem MF, Cortés-Hinojosa G, Kennedy-Stoskopf S. CRC Handbook of Marine Mammal Medicine. Boca Raton, FL: CRC Press; (2018). p. 332–51. [PubMed]
- 18. Simpson VR, Stuart NC, Stack MJ, Ross HA, Head JC. Parapox infection in grey seals (Halichoerus grypus) in Cornwall. Vet Rec. (1994) 134:292–6. 10.1136/vr.134.12.292 [] [[PubMed]
- 19. Clark C, McIntyre PG, Evans A, McInnes CJ, Lewis-Jones S. Human sealpox resulting from a seal bite: confirmation that sealpox virus is zoonotic. Br J Dermatol. (2005) 152:791–3. 10.1111/j.1365-2133.2005.06451.x [] [[PubMed]
- 20. Wilson TM, Sweeney PR. Morphological studies of seal poxvirus. J Wild Dis. (1970) 6:94–7. 10.7589/0090-3558-6.2.94 [] [[PubMed]
- 21. Nollens HH, Gulland FMD, Jacobson ER, Hernandez JA, Klein PA, Walsh MT, et al. . Parapoxviruses of seals and sea lions make up a distinct subclade within the genus parapoxvirus. Virol J. (2006) 349:316–24. 10.1016/j.virol.2006.01.020 [] [[PubMed]
- 22. Inoshima Y, Morooka A, Sentsui H. Detection and diagnosis of parapoxvirus by the polymerase chain reaction. J Virol Methods. (2000) 84:201–8. 10.1016/S0166-0934(99)00144-5 [] [[PubMed]
- 23. Hautaniemi M, Ueda N, Tuimala J, Mercer AA, Lahdenperä J, McInnes CJ. The genome of pseudocowpoxvirus: comparison of a reindeer isolate and a reference strain. J General Virol. (2010) 91:1560–76. 10.1099/vir.0.018374-0 [] [[PubMed]
- 24. Haller SL, Peng C, McFadden G, Rothenburg S. Poxviruses and the evolution of host range and virulence. Infect Genet Evol. (2014) 21:15–40. 10.1016/j.meegid.2013.10.014 ] [
- 25. Deane D, McInnes CJ, Percival A, Wood A, Thomson J, Lear A, et al. . Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and interleukin-2. J Virol. (2000) 74:1313–20. 10.1128/JVI.74.3.1313-1320.2000 ] [
- 26. Fleming SB, Anderson IE, Thomson J, Deane DL, McInnes CJ, McCaughan CA, et al. . Infection with recombinant orf viruses demonstrates that the viral interleukin-10 is a virulence factor. J Gen Virol. (2007) 88:1922–27. 10.1099/vir.0.82833-0 [] [[PubMed]
- 27. Klein J, Tryland M. Characterization of parapoxviruses isolated from Norwegian semi-domesticated reindeer (Rangifer tarandus tarandus). Virol J. (2005) 2:1–10. 10.1186/1743-422X-2-79 ] [
- 28. Bracht AJ, Brudek RL, Ewing RY, Manire CA, Burek KA, Rosa C, et al. . Genetic identification of novel poxviruses of cetaceans and pinnipeds. Arch Virol. (2006) 151:423–38. 10.1007/s00705-005-0679-6 [] [[PubMed]
- 29. GENBANK, National Center for Biotechnology, Information National Library of Medicine National Institutes of Health. Available online at: (accessed December 10, 2020).
- 30. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Bio Evol. (2018) 35:1547–9. 10.1093/molbev/msy096 ] [
- 31. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. (1987) 4:406–25. [[PubMed]
- 32. Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. (1980) 16:111–20. 10.1007/BF01731581 [] [[PubMed]
- 33. Núñez-Egido S, Lowther A, Nymo IH, Klein J, Breines EM, Tryland M. Pathogen surveillance in Southern Ocean pinnipeds. Polar Res. (2020) 39:3841. 10.33265/polar.v39.3841 [[PubMed]
- 34. Scotter SE, Tryland M, Nymo IH, Hanssen L, Fisk AT, Harju M, et al. . Contaminants in Atlantic walruses in Svalbard part 1: relationships between exposure, diet and pathogen prevalence. Environ Pollut. (2019) 244:9–18. 10.1016/j.envpol.2018.10.001 [] [[PubMed]
- 35. Deane D, Ueda N, Wise LM, Wood AR, Percival A, Jepson C, et al. . Conservation and variation of the parapoxvirus GM-CSF-inhibitory factor (GIF) proteins. J Gen Virol. (2009) 90:970–7. 10.1099/vir.0.006692-0 [] [[PubMed]
- 36. Moyer RW, Turner PC. Poxviruses. Current Topics in Microbiology and Immunology. Berlin: Springer Science & Business Media; (1990). [PubMed]
- 37. Rziha HJ, Henkel M, Cottone R, Meyer M, Dehio C, Büttner M. Parapoxviruses: potential alternative vectors for directing the immune response in permissive and non-permissive hosts. J Biotechnol. (1999) 73:235–42. 10.1016/S0168-1656(99)00141-8 [] [[PubMed]
- 38. Tryland M. Zoonoses and public health. In: Gulland FMD, Dierauf LA, Whitman KL. editors. Handbook of Marine Mammal Medicine. Boca Raton, FL: CRC Press; (2018). p. 47–61. [PubMed]