, Volume 8, Issue 3, pp 301–319 | Cite as

Phylogeny, Life History, and Ecology Contribute to Differences in Amphibian Susceptibility to Ranaviruses

  • Jason T. HovermanEmail author
  • Matthew J. Gray
  • Nathan A. Haislip
  • Debra L. Miller
Original Contribution


Research that identifies the potential host range of generalist pathogens as well as variation in host susceptibility is critical for understanding and predicting the dynamics of infectious diseases within ecological communities. Ranaviruses have been linked to amphibian die-off events worldwide with the greatest number of reported mortality events occurring in the United States. While reports of ranavirus-associated mortality events continue to accumulate, few data exist comparing the relative susceptibility of different species. Using a series of laboratory exposure experiments and comparative phylogenetics, we compared the susceptibilities of 19 amphibian species from two salamander families and five anurans families for two ranavirus isolates: frog virus 3 (FV3) and an FV3-like isolate from an American bullfrog culture facility. We discovered that ranaviruses were capable of infecting 17 of the 19 larval amphibian species tested with mortality ranging from 0 to 100%. Phylogenetic comparative methods demonstrated that species within the anuran family Ranidae were generally more susceptible to ranavirus infection compared to species from the other five families. We also found that susceptibility to infection was associated with species that breed in semi-permanent ponds, develop rapidly as larvae, and have limited range sizes. Collectively, these results suggest that phylogeny, life history characteristics, and habitat associations of amphibians have the potential to impact susceptibility to ranaviruses.


Anura Caudata Emerging infectious disease Frog virus 3 Iridoviridae Novel strain Phylogeny Reservoir 



We thank the University of Georgia Veterinary Diagnostic and Investigational Laboratory, University of Tennessee Institute of Agriculture, and Tennessee Wildlife Resources Agency (TWRA) for funding this study. We thank C. Baldwin and D. Ingram for providing the virus isolate; N. Hilzinger and L. Whittington for conducting the PCR; and J. Hodges, B. Simpson, M. Campbell, and R. Long for various resources at JARTU. We also thank R. Relyea, J. Hammond, and J. Davenport for providing several species for the experiments. P. Stephens provided insightful comments on the phylogenetic methods. The P. Johnson Lab at the University of Colorado provided helpful feedback on initial drafts of the manuscript. We thank J. Rohr and several anonymous reviewers for helpful comments on the manuscript. All animal husbandry and euthanasia procedures followed an approved University of Tennessee IACUC protocol (#1755). Collection of egg masses was approved by the TWRA (Scientific Collection Permit #1990).


  1. Begon M (2008) Effects of host diversity on disease dynamics. In: Infectious Disease Ecology: The Effects of Ecosystems on Disease and of Disease on Ecosystems, Ostfeld R, Keesing F, Eviner VT (editors), Princeton, NJ: Princeton University Press, pp 12–29.Google Scholar
  2. Blomberg SP, Garland T, and Ives AR (2003). Testing for phylogenetic signal in comparative data: Behavioral traits are more labile. Evolution 57:717-745.PubMedGoogle Scholar
  3. Bollinger TK, Mao JH, Schock D, Brigham RM, and Chinchar VG (1999). Pathology, isolation, and preliminary molecular characterization of a novel iridovirus from tiger salamanders in Saskatchewan. Journal of Wildlife Diseases 35:413-429.PubMedGoogle Scholar
  4. Brunner JL, Barnett KE, Gosier CJ, McNulty SA, Rubbo MJ, and Kolozsvary MB (2011). Ranavirus infection in die-offs of vernal pool amphibians in New York, USA. Herpetological Review 42:76-79.Google Scholar
  5. Brunner JL, Richards K, and Collins JP (2005). Dose and host characteristics influence virulence of ranavirus infections. Oecologia 144:399-406.PubMedCrossRefGoogle Scholar
  6. Brunner JL, Schock DM, and Collins JP (2007). Transmission dynamics of the amphibian ranavirus Ambystoma tigrinum virus. Diseases of Aquatic Organisms 77:87-95.PubMedCrossRefGoogle Scholar
  7. Bryan L, Baldwin CA, Gray MJ, and Miller DL (2009). Efficacy of select disinfectants at inactivating Ranavirus. Diseases of Aquatic Organisms 84:89-94.PubMedCrossRefGoogle Scholar
  8. Carey C, Bradford DE, Brunner JL, Collins JP, et al. (2003) Biotic factors in amphibian declines. In: Amphibian Declines: An Integrated Analysis of Multiple Stressor Effects. Pensacola, FL: Society of Environmental Toxicology and Chemistry, pp 153–208.Google Scholar
  9. Collinge SK, and Ray C (2006). Disease ecology: community structure and pathogen dynamics. Oxford University Press.Google Scholar
  10. Conant R, and Collins J (1998). A field guide to reptiles and amphibians of eastern and central North America, 3rd edition. Houghton Mifflin, Boston.Google Scholar
  11. Converse KA, and Green DE (2005). Diseases of tadpoles. Pages 72-88 in S. K. Majumdar, J. E. Huffman, F. J. Brenner, and A. I. Panah, editors. Wildlife diseases: Landscape epidemiology, spatial distribution and utilization of remote sensing technology. The Pennsylvania Academy of Science, Easton, Pennsylvania.Google Scholar
  12. Craft ME, Hawthorne PL, Packer C, and Dobson AP (2008). Dynamics of a multihost pathogen in a carnivore community. Journal of Animal Ecology 77:1257-1264.PubMedCrossRefGoogle Scholar
  13. Cronin JP, Welsh ME, Dekkers MG, Abercrombie ST, and Mitchell CE (2010). Host physiological phenotype explains pathogen reservoir potential. Ecology Letters 13:1221-1232.PubMedCrossRefGoogle Scholar
  14. Cunningham AA, Hyatt AD, Russell P, and Bennett PM (2007). Emerging epidemic diseases of frogs in Britain are dependent on the source of ranavirus agent and the route of exposure. Epidemiology and Infection 135:1200-1212.PubMedGoogle Scholar
  15. Daszak P, Berger L, Cunningham AA, Hyatt AD, Green DE, and Speare R (1999). Emerging infectious diseases and amphibian population declines. Emerging Infectious Diseases 5:735-748.PubMedCrossRefGoogle Scholar
  16. Daszak P, Cunningham AA, and Hyatt AD (2000). Wildlife ecology - Emerging infectious diseases of wildlife: threats to biodiversity and human health. Science 287:443-449.PubMedCrossRefGoogle Scholar
  17. Dobson A, and Foufopoulos J (2001). Emerging infectious pathogens of wildlife. Philosophical Transactions of the Royal Society of London Series B-Biological Sciences 356:1001-1012.CrossRefGoogle Scholar
  18. Docherty DE, Meteyer CU, Wang J, Mao JH, Case ST, and Chinchar VG (2003). Diagnostic and molecular evaluation of three iridovirus-associated salamander mortality events. Journal of Wildlife Diseases 39:556-566.PubMedGoogle Scholar
  19. Duffus ALJ, Pauli BD, Wozney K, Brunetti CR, and Berrill M (2008). Frog virus 3-like infections in aquatic amphibian communities. Journal of Wildlife Diseases 44:109-120.PubMedGoogle Scholar
  20. Elliot L, Gerhardt HC, and Davidson C (2009). The frogs and toads of North America: A comprehensive guide to their identification, behavior, and calls. Houghton Mifflin Company, Boston, MA.Google Scholar
  21. Felsenstein J (1985). Phylogenies and the comparative method. American Naturalist 125:1-15.CrossRefGoogle Scholar
  22. Gahl MK, and Calhoun AJK (2008). Landscape setting and risk of Ranavirus mortality events. Biological Conservation 141:2679-2689.CrossRefGoogle Scholar
  23. Gantress J, Maniero GD, Cohen N, and Robert J (2003). Development and characterization of a model system to study amphibian immune responses to iridoviruses. Virology 311:254-262.PubMedCrossRefGoogle Scholar
  24. Garland T, Harvey PH, and Ives AR (1992). Procedures for the analysis of comparative data using phylogenetically independent contrasts. Systematic Biology 41:18-32.Google Scholar
  25. Gosner KL (1960). A simplified table for staging anuran embryos and larvae with notes and identification. Herpetologica 16:183-190.Google Scholar
  26. Granoff A, Came PE, and Rafferty KA (1965). The isolation and properties of viruses from Rana pipiens: Their possible relationship to the renal adenocarcinoma of the leopard frog. Annals of the new York Academy of Science 126:237-255.CrossRefGoogle Scholar
  27. Gray MJ, Miller DL, and Hoverman JT (2009). Ecology and pathology of amphibian ranaviruses. Diseases of Aquatic Organisms 87:243-266.PubMedCrossRefGoogle Scholar
  28. Green DE, Converse KA, and Schrader AK (2002). Epizootiology of sixty-four amphibian morbidity and mortality events in the USA, 1996-2001. Annals of the New York Academy of Sciences 969:323-339.PubMedCrossRefGoogle Scholar
  29. Greer AL, Berrill M, and Wilson PJ (2005). Five amphibian mortality events associated with ranavirus infection in south central Ontario, Canada. Diseases of Aquatic Organisms 67:9-14.PubMedCrossRefGoogle Scholar
  30. Haislip NA, Gray MJ, Hoverman JT, and Miller DL (2011). Development and disease: How susceptibility to an emerging pathogen changes through anuran development. Plos One 6:e22307.PubMedCrossRefGoogle Scholar
  31. Harp EM, and Petranka JW (2006). Ranavirus in wood frogs (Rana sylvatica): Potential sources of transmission within and between ponds. Journal of Wildlife Diseases 42:307-318.PubMedGoogle Scholar
  32. Harvey PH, and Pagel M (1991). The comparative method in evolutionary biology. Oxford University Press, Oxford.Google Scholar
  33. Hedges SB, Dudley J, and Kumar S (2006). TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 22:2971-2972.PubMedCrossRefGoogle Scholar
  34. Hillis DM, and Wilcox TP (2005). Phylogeny of the New World true frogs (Rana). Molecular Phylogenetics and Evolution 34:299-314.PubMedCrossRefGoogle Scholar
  35. Houlahan JE, Findlay CS, Meyer AH, Kuzmin SL, and Schmidt BR (2001). Ecology - Global amphibian population declines - Reply. Nature 412:500-500.CrossRefGoogle Scholar
  36. Hoverman JT, Gray MJ, and Miller DL (2010). Anuran susceptibilities to ranaviruses: role of species identity, exposure route, and a novel virus isolate. Diseases of Aquatic Organisms 89:97-107.PubMedCrossRefGoogle Scholar
  37. Jancovich JK, Davidson EW, Morado JF, Jacobs BL, and Collins JP (1997). Isolation of a lethal virus from the endangered tiger salamander Ambystoma tigrinum stebbinsi. Diseases of Aquatic Organisms 31:161-167.CrossRefGoogle Scholar
  38. Kerby JL, and Storfer A (2009). Combined Effects of Atrazine and Chlorpyrifos on Susceptibility of the Tiger Salamander to Ambystoma tigrinum Virus. Ecohealth 6:91-98.PubMedCrossRefGoogle Scholar
  39. Lannoo M (2005). Amphibian declines: the conservation status of United States species. University of California Press, Berkeley, California.Google Scholar
  40. Lemmon EM, Lemmon AR, and Cannatella DC (2007). Geological and climatic forces driving speciation in the continentally distributed trilling chorus frogs (Pseudacris). Evolution 61:2086-2103.PubMedCrossRefGoogle Scholar
  41. Lochmiller RL, and Deerenberg C (2000). Trade-offs in evolutionary immunology: just what is the cost of immunity? Oikos 88:87-98.CrossRefGoogle Scholar
  42. Martins EP (2004) COMPARE, version 4.6b. Computer programs for the statistical analysis of comparative data. Distributed by the author at Bloomington, IN: Department of Biology, Indiana University.
  43. Miller DL, Rajeev S, Gray MJ, and Baldwin CA (2007a). Frog virus 3 infection, cultured American bullfrogs. Emerging Infectious Diseases 13:342-343.PubMedCrossRefGoogle Scholar
  44. Miller MR, White A, and Boots M (2007b). Host life span and the evolution of resistance characteristics. Evolution 61:2-14.PubMedCrossRefGoogle Scholar
  45. Morales HD, and Robert J (2007). Characterization of primary and memory CD8 T-cell responses against ranavirus (FV3) in Xenopus laevis. Journal Of Virology 81:2240-2248.PubMedCrossRefGoogle Scholar
  46. Muths E, Gallant AL, Campbell EHC, Battaglin WA, Green DE, Staiger JS, et al. (2006) The Amphibian Research and Monitoring Initiative (ARMI): 5-year Report: U.S. Geological Survey Scientific Investigations Report 2006-5224.Google Scholar
  47. Ord TJ, and Martins EP (2006). Tracing the origins of signal diversity in anole lizards: phylogenetic approaches to inferring the evolution of complex behaviour. Animal Behaviour 71:1411-1429.CrossRefGoogle Scholar
  48. Ostfeld R, Keesing F, and Eviner VT (2008). Infectious disease ecology: the effects of ecosystems on disease and of disease on ecosystems. Princeton University Press, Princeton, N.J.Google Scholar
  49. Pearman PB, and Garner TWJ (2005). Susceptibility of Italian agile frog populations to an emerging strain of Ranavirus parallels population genetic diversity. Ecology Letters 8:401-408.CrossRefGoogle Scholar
  50. Pearman PB, Garner TWJ, Straub M, and Greber UF (2004). Response of the Italian agile frog (Rana latastei) to a Ranavirus, Frog Virus 3: a model for viral emergence in naïve populations. Journal of Wildlife Diseases 40:660-669.PubMedGoogle Scholar
  51. Pedersen AB, and Fenton A (2007). Emphasizing the ecology in parasite community ecology. Trends in Ecology & Evolution 22:133-139.CrossRefGoogle Scholar
  52. Petranka JW (1998). Salamanders of the United States and Canada. Smithsonian Institution Press, Washington, DC.Google Scholar
  53. Petranka JW, Harp EM, Holbrook CT, and Hamel JA (2007). Long-term persistence of amphibian populations in a restored wetland complex. Biological Conservation 138:371-380.CrossRefGoogle Scholar
  54. Petranka JW, Murray SS, and Kennedy CA (2003). Responses of amphibians to restoration of a southern appalachian wetland: Perturbations confound post-restoration assessment. Wetlands 23:278-290.CrossRefGoogle Scholar
  55. Picco AM, Brunner JL, and Collins JP (2007). Susceptibility of the endangered California tiger salamander, Ambystoma californiense, to Ranavirus infection. Journal of Wildlife Diseases 43:286-290.PubMedGoogle Scholar
  56. Price T, Lovette IJ, Bermingham E, Gibbs HL, and Richman AD (2000). The imprint of history on communities of North American and Asian warblers. American Naturalist 156:354-367.CrossRefGoogle Scholar
  57. Pyke DA, and Thompson JN (1986). Statistical analysis of survival and removal expeiments. Ecology 67:240-245.CrossRefGoogle Scholar
  58. R_Development_Core_Team (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0,
  59. Relyea RA (2002). Competitor-induced plasticity in tadpoles: Consequences, cues, and connections to predator-induced plasticity. Ecological Monographs 72:523-540.CrossRefGoogle Scholar
  60. Rigaud T, Perrot-Minnot MJ, and Brown MJF (2010). Parasite and host assemblages: embracing the reality will improve our knowledge of parasite transmission and virulence. Proceedings of the Royal Society B-Biological Sciences 277:3693-3702.CrossRefGoogle Scholar
  61. Schock D, Bollinger TK, and Collins JP (2009). Mortality rates differ among amphibian populations exposed to three strains of a lethal ranavirus. Ecohealth 6:438-448.PubMedCrossRefGoogle Scholar
  62. Schock DM, and Bollinger TK (2005). An apparent decline of Northern Leopard Frogs (Rana pipiens) on the Rafferty Dam Mitigation Lands near Estevan, Saskatchewan. Blue Jay 63:144-154.Google Scholar
  63. Schock DM, Bollinger TK, Chinchar VG, Jancovich JK, Collins JP (2008) Experimental evidence that amphibian ranaviruses are multi-host pathogens. Copeia 133–143.Google Scholar
  64. Searle CL, Gervasi SS, Hua J, Hammond JI, Relyea RA, Olson DH, et al. (2011). Differential host susceptibility to Batrachochytrium dendrobatidis, an emerging amphibian pathogen. Conservation Biology 25(1):965–974.PubMedCrossRefGoogle Scholar
  65. Shaffer HB, Clark JM, and Kraus F (1991). When molecules and morphology clash - A phylogenetic analysis of the North American ambystomatid salamanders (Caudata, Ambystomatidae). Systematic Zoology 40:284-303.CrossRefGoogle Scholar
  66. Stephens PR, and Wiens JJ (2004). Convergence, divergence, and homogenization in the ecological structure of emydid turtle communities: the effects of phylogeny and dispersal. American Naturalist 164:244-254.PubMedCrossRefGoogle Scholar
  67. Stephens PR, and Wiens JJ (2008). Testing for evolutionary trade-offs in a phylogenetic context: ecological diversification and evolution of locomotor performance in emydid turtles. Journal of Evolutionary Biology 21:77-87.PubMedGoogle Scholar
  68. Stuart SN, Chanson JS, Cox NA, Young BE, Rodrigues ASL, Fischman DL, et al. (2004). Status and trends of amphibian declines and extinctions worldwide. Science 306:1783-1786.PubMedCrossRefGoogle Scholar
  69. Telfer S, Birtles R, Bennett M, Lambin X, Paterson S, and Begon M (2008). Parasite interactions in natural populations: insights from longitudinal data. Parasitology 135:767-781.PubMedCrossRefGoogle Scholar
  70. Torrence SM, Green DE, Benson CJ, Ip HS, Smith LM, and McMurry ST (2010). A New Ranavirus Isolated from Pseudacris clarkii Tadpoles in Playa Wetlands in the Southern High Plains, Texas. Journal of Aquatic Animal Health 22:65-72.PubMedCrossRefGoogle Scholar
  71. Tweedell K, and Granoff A (1968). Viruses and renal carcinoma of Rana pipiens. V. Effect of Frog Virus 3 on developing frog embryos and larvae. Journal of the National Cancer Institute 40:407-410.PubMedGoogle Scholar
  72. Wake DB, and Vredenburg VT (2008). Are we in the midst of the sixth mass extinction? A view from the world of amphibians. Proceedings of the National Academy of Sciences 105:11466-11473.CrossRefGoogle Scholar
  73. Warne RW, Crespi EJ, and Brunner JL (2011). Escape from the pond: stress and developmental responses to ranavirus infection in wood frog tadpoles. Functional Ecology 25:139-146.CrossRefGoogle Scholar
  74. Wellborn GA, Skelly DK, and Werner EE (1996). Mechanisms creating community structure across a freshwater habitat gradient. Annual Review of Ecology and Systematics 27:337-363.CrossRefGoogle Scholar
  75. Wells KD (2007). The ecology and behavior of amphibians. The University of Chicago Press, Chicago.Google Scholar
  76. Werner EE, Skelly DK, Relyea RA, and Yurewicz KL (2007a). Amphibian species richness across environmental gradients. Oikos 116:1697-1712.CrossRefGoogle Scholar
  77. Werner EE, Yurewicz KL, Skelly DK, and Relyea RA (2007b). Turnover in an amphibian metacommunity: the role of local and regional factors. Oikos 116:1713-1725.CrossRefGoogle Scholar
  78. Wiens JJ, Fetzner JW, Parkinson CL, and Reeder TW (2005). Hylid frog phylogeny and sampling strategies for speciose clades. Systematic Biology 54:719-748.CrossRefGoogle Scholar
  79. Woolhouse MEJ, and Gowtage-Sequeria S (2005). Host range and emerging and reemerging pathogens. Emerging Infectious Diseases 11:1842-1847.PubMedCrossRefGoogle Scholar
  80. Zuk M, and Stoehr AM (2002). Immune defense and host life history. American Naturalist 160:S9-S22.PubMedCrossRefGoogle Scholar

Copyright information

© International Association for Ecology and Health 2011

Authors and Affiliations

  • Jason T. Hoverman
    • 1
    • 2
    Email author
  • Matthew J. Gray
    • 2
  • Nathan A. Haislip
    • 2
    • 4
  • Debra L. Miller
    • 2
    • 3
    • 5
  1. 1.Department of Ecology and Evolutionary BiologyUniversity of ColoradoBoulderUSA
  2. 2.Center for Wildlife Health, Department of Forestry, Wildlife, and FisheriesUniversity of TennesseeKnoxvilleUSA
  3. 3.Veterinary Diagnostic and Investigational Laboratory, College of Veterinary MedicineUniversity of GeorgiaGeorgiaUSA
  4. 4.Department of EctothermsFort Worth ZooFort WorthUSA
  5. 5.Department of Biomedical and Diagnostic Sciences, College of Veterinary MedicineUniversity of TennesseeKnoxvilleUSA

Personalised recommendations