04533naa a2200445 a 450000100080000000500110000800800410001902200140006002400270007410000180010124501990011926000090031850009270032752022510125465300130350565300110351865300220352965300300355165300160358165300310359765300140362865300490364265300170369165300260370865300190373470000190375370000160377270000140378870000270380270000270382970000260385670000230388270000160390570000160392170000160393770000150395370000170396870000170398577300850400210636412022-10-06       2022    bl uuuu     u00u1 u    #d  a1999-49157 a10.3390/v140920422DOI1 aGIANNITTI, F.  aBovine Polyomavirus-1 (Epsilonpolyomavirus bovis)bAn emerging fetal pathogen of cattle that causes renal lesions resembling Polyomavirus-associated nephropathy of humans.h[electronic resource]  c2022  aArticle history: Received 12 August 2022; Revised 8 September 2022: Accepted 9 September 2022; Published 14 September 2022.  Academic Editors: Fernando Bauermann and Mayara Maggioli. Correspondence authors: Giannitti, F.; Plataforma de Investigación en Salud Animal, Instituto Nacional de Investigación Agropecuaria (INIA), Estación Experimental La Estanzuela, Colonia, Uruguay; email:fgiannitti@inia.org.uy - Castells, M.; Laboratorio de Virología Molecular, Departamento de Ciencias Biológicas, Centro Universitario Regional (CENUR) Litoral Norte, Universidad de la República, Salto, Uruguay; email:matiascastellsbauer@gmail.com  --   Funding: Instituto Nacional de Investigación Agropecuaria (INIA), grant PL_27 N-23398. -- This article belongs to the Special Issue Pathogenesis and Host Responses to Viral Diseases in Livestock Species: https://www.mdpi.com/journal/viruses/special_issues/pathogenesis_livestock  aABSTRACT.- 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 a 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. © 2022 by the authors.  aAbortion  aCattle  aEmerging diseases  aEpsilonpolyomavirus bovis  aNephropathy  aNext generation sequencing  aPathology  aPLATAFORMA DE INVESTIGACIÓN EN SALUD ANIMAL  aPolyomavirus  aReproductive diseases  aViral diseases1 aSILVEIRA, C.S.1 aBULLOCK, H.1 aBERON, M.1 aFERNÁNDEZ-CIGANDA, S.1 aBENÍTEZ-GALEANO, M.J.1 aRODRÍGUEZ-OSORIO, N.1 aSILVA-FLANNERY, L.1 aPERDOMO, T.1 aCABRERA, A.1 aPUENTES, R.1 aCOLINA, R.1 aRITTER, J.M.1 aCASTELLS, M.  tViruses, 2022; 14 (9): 2042. OPEN ACCESS. doi: https://doi.org/10.3390/v14092042