UC Davis

Until recently, the genus Amdoparvovirus (family: Parvoviridae) was considered monotypic, comprising only a single recognized viral species. Aleutian Mink Disease Virus (AMDV), the type species, emerged as a significant pathogen on mink farms in the 1950s, and has been relatively well studied due to its economic importance. Despite decades of AMDV research, the pathogenesis and determinants of disease manifestation are still incompletely understood, and no effective treatment or preventative (vaccine) exists. New Amdoparvoviruses have since been discovered in several additional small carnivore species, primarily among the Mustelidae, Canidae, and Ailuridae. These discoveries have indicated a broad range of potentially susceptible host species, but the epidemiology and pathologic consequences of these infections are not well understood. Skunk Amdoparvovirus (SKAV) was first reported in free-ranging striped skunks (Mephitis Mephitis) in Canada in 2017, and Red Panda Amdoparvovirus (RPAV) was first reported in a cohort of endangered western red pandas (Ailurus fulgens) at a zoological institution in the USA in 2018. These novel viruses offer unique opportunities to examine the impact of Amdoparvovirus infections across species, and outside of the context of a mink farm. We undertook a series of studies to evaluate the impact of SKAV and RPAV in their respective hosts. We evaluated the prevalence of Amdoparvovirus infections in these heretofore unrecognized hosts by prospective sampling of tissues from necropsied animals and feces from living zoo-housed red pandas. The long-term management of red pandas in zoos also provided an opportunity evaluate evidence of viral persistence in individual animals based on detection and quantitation in fecal samples, which were collected prospectively over a six-year timespan. To understand the relationships among Amdoparvoviruses within and between host species, we performed phylogenetic analyses on viral sequences obtained from prevalence studies. Finally, we evaluated tissue targets and the spectrum of Amdoparvovirus-associated lesions using in situ hybridization assays to localize viral nucleic acid in archived, formalin-fixed, paraffin-embedded tissues collected during necropsies. SKAV appears to be an ancient but previously unrecognized virus in striped skunks, with infections detectable across their North American range and significant sequence variation largely attributable to geographic origin of samples. RPAV was likewise detected in zoological collections across the United States, and exhibits marked sequence variation. Three distinct clades of RPAV appear to circulate in the North American zoo-housed population, and are likely transmitted among cohorts by inter-institutional transfers for breeding or management purposes. Both SKAV and RPAV appear to infect a variety of host cell targets, including epithelium, endothelium, and leukocytes, and although asymptomatic infections appear to be common, both viruses were associated with lesions in some cases, including tubulointerstitial nephritis, myocarditis, and arteritis. We conclude that persistent Amdoparvovirus infections, while previously unrecognized, are widespread and potentially important pathogens in these hosts. An additional study to evaluate potential viral etiologies in cases of encephalitis in American black bears (Ursus americanus) is also described in this thesis. Novel viruses – including a novel circovirus and a novel Chapahamaparvovirus – were detected in this study, although a specific etiologic association with lesions was not definitively identified. The approach to evaluating clinical significance of a novel and potentially pathogenic virus is the same, underscoring the importance of retrospective and prospective evaluations and the challenges associated with establishing disease causality in the context of persistent viruses.