title: Pathogenesis of Frog Virus 3 ( Ranavirus, Iridoviridae) Infection in Wood Frogs ( Rana sylvatica).
abstract: Wood frogs ( Rana sylvatica) are highly susceptible to infection with Frog virus 3 (FV3, Ranavirus, Iridoviridae), a cause of mass mortality in wild populations. To elucidate the pathogenesis of FV3 infection in wood frogs, 40 wild-caught adults were acclimated to captivity, inoculated orally with a fatal dose of 104.43pfu/frog, and euthanized at 0.25, 0.5, 1, 2, 4, 9, and 14 days postinfection (dpi). Mild lesions occurred sporadically in the skin (petechiae) and bone marrow (necrosis) during the first 2 dpi. Severe lesions occurred 1 to 2 weeks postinfection and consisted of necrosis of medullary and extramedullary hematopoietic tissue, lymphoid tissue in spleen and throughout the body, and epithelium of skin, mucosae, and renal tubules. Viral DNA was first detected (polymerase chain reaction) in liver at 4 dpi; by dpi 9 and 14, all viscera tested (liver, kidney, and spleen), skin, and feces were positive. Immunohistochemistry (IHC) first detected viral antigen in small areas devoid of histologic lesions in the oral mucosa, lung, and colon at 4 dpi; by 9 and 14 dpi, IHC labeling of viral antigen associated with necrosis was found in multiple tissues. Based on IHC staining intensity and lesion severity, the skin, oral, and gastrointestinal epithelium and renal tubular epithelium were important sites of viral replication and shedding, suggesting that direct contact (skin) and fecal-oral contamination are effective routes of transmission and that skin tissue, oral, and cloacal swabs may be appropriate antemortem diagnostic samples in late stages of disease (>1 week postinfection) but poor samples to detect infection in clinically healthy frogs.
authors.affiliation: 1 Canadian Wildlife Health Cooperative, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.|2 Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Forzán
authors.affiliation: 2 Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: K M
authors.initials: KM
authors.lastname: Jones
authors.affiliation: 3 College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Ariel
authors.affiliation: 4 School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Camden, New South Wales, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Whittington
authors.affiliation: 5 Pisces Molecular LLC, Boulder, CO, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wood
authors.affiliation: 2 Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: R J Frederick
authors.initials: RJF
authors.lastname: Markham
authors.affiliation: 1 Canadian Wildlife Health Cooperative, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.|2 Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Daoust
mesh_terms: D000818:Animals; D000835:Animals, Wild / Q000821:virology; D004266:DNA Virus Infections / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D008297:Male; D017995:Ranavirus / Q000472:pathogenicity; D011898:Ranidae / Q000235:genetics / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
keywords: Frog virus 3; Lithobates sylvaticus; Rana sylvatica; Ranavirus; pathogenesis; wood frog