title: Clinical signs, pathology and dose-dependent survival of adult wood frogs, Rana sylvatica, inoculated orally with frog virus 3 Ranavirus sp., Iridoviridae.
abstract: Amphibian populations suffer massive mortalities from infection with frog virus 3 FV3, genus Ranavirus, family Iridoviridae, a pathogen also involved in mortalities of fish and reptiles. Experimental oral infection with FV3 in captive-raised adult wood frogs, Rana sylvatica Lithobates sylvaticus, was performed as the first step in establishing a native North American animal model of ranaviral disease to study pathogenesis and host response. Oral dosing was successful LD50 was 10(2.93 2.423.44) p.f.u. for frogs averaging 35mm in length. Onset of clinical signs occurred 614days post-infection p.i. median 11 days p.i. and time to death was 1014 days p.i. median 12 days p.i.. Each tenfold increase in virus dose increased the odds of dying by 23-fold and accelerated onset of clinical signs and death by approximately 15. Ranavirus DNA was demonstrated in skin and liver of all frogs that died or were euthanized because of severe clinical signs. Shedding of virus occurred in faeces 710 days p.i. 34.5days before death and skin sheds 10 days p.i. 01.5days before death of some frogs dead from infection. Most common lesions were dermal erosion and haemorrhages haematopoietic necrosis in bone marrow, kidney, spleen and liver and necrosis in renal glomeruli, tongue, gastrointestinal tract and urinary bladder mucosa. Presence of ranavirus in lesions was confirmed by immunohistochemistry. Intracytoplasmic inclusion bodies probably viral were present in the bone marrow and the epithelia of the oral cavity, gastrointestinal tract, renal tubules and urinary bladder. Our work describes a ranaviruswood frog model and provides estimates that can be incorporated into ranavirus disease ecology models.
authors.affiliation: Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Canada.|Canadian Wildlife Health Cooperative.
authors.forename: María J
authors.initials: MJ
authors.lastname: Forzán
authors.affiliation: Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Canada.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Jones
authors.affiliation: Department of Health Management, Atlantic Veterinary College, University of Prince Edward Island, Canada.
authors.forename: Raphaël V
authors.initials: RV
authors.lastname: Vanderstichel
authors.affiliation: Pisces Molecular LLC, Boulder, Colorado, USA.
authors.forename: John
authors.initials: J
authors.lastname: Wood
authors.affiliation: Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Canada.
authors.forename: Frederick S B
authors.initials: FSB
authors.lastname: Kibenge
authors.affiliation: Department of Viroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.affiliation: School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Australia.
authors.forename: Wytamma
authors.initials: W
authors.lastname: Wirth
authors.affiliation: School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Australia.
authors.forename: Ellen
authors.initials: E
authors.lastname: Ariel
authors.affiliation: Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Canada.|Canadian Wildlife Health Cooperative.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Daoust
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000821:virology; D004266:DNA Virus Infections / Q000401:mortality / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D004279:DNA, Viral / Q000302:isolation & purification; D005243:Feces / Q000821:virology; D007668:Kidney / Q000473:pathology / Q000821:virology; D007928:Lethal Dose 50; D008099:Liver / Q000473:pathology / Q000821:virology; D017995:Ranavirus / Q000254:growth & development* / Q000302:isolation & purification; D011898:Ranidae / Q000821:virology*; D012867:Skin / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D017201:Virus Shedding
chemical_list: D004279:DNA, Viral