Bovine polyomavirus-1 (Epsilonpolyomavirus bovis): An emerging fetal pathogen of cattle that causes renal lesions resembling polyomavirus-associated nephropathy of humans

Abstract

Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1-associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed. Author SummaryWhile bovine polyomavirus-1 seems to have a broad geographic distribution, whether this virus is responsible for disease and organ damage (lesions) in the cattle it infects is unknown. In this study, we describe and illustrate organ damage in an aborted bovine fetus naturally infected with bovine polyomavirus-1. Our results indicate that this virus is pathogenic, this means it can cause lesions and disease under natural circumstances in cattle. Interestingly, the organ damage in the fetus attributable to this viral infection closely resembles the lesions caused by related viruses within the same viral family (Polyomaviridae) in immunocompromised human patients and kidney transplant recipients. This study sets the bases to frame further research to learn more about whether bovine polyomavirus-1 causes abortion in cattle, and to a broader extent how polyomaviruses cause disease in animals and humans.