<i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans

<i>Bovine polyomavirus-1</i> (BoPyV-1, <i>Epsilonpolyomavirus bovis</i>) 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 seroposit...

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Main Authors: Federico Giannitti, Caroline da Silva Silveira, Hannah Bullock, Marina Berón, Sofía Fernández-Ciganda, María José Benítez-Galeano, Nélida Rodríguez-Osorio, Luciana Silva-Flannery, Yisell Perdomo, Andrés Cabrera, Rodrigo Puentes, Rodney Colina, Jana M. Ritter, Matías Castells
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/14/9/2042
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author Federico Giannitti
Caroline da Silva Silveira
Hannah Bullock
Marina Berón
Sofía Fernández-Ciganda
María José Benítez-Galeano
Nélida Rodríguez-Osorio
Luciana Silva-Flannery
Yisell Perdomo
Andrés Cabrera
Rodrigo Puentes
Rodney Colina
Jana M. Ritter
Matías Castells
author_facet Federico Giannitti
Caroline da Silva Silveira
Hannah Bullock
Marina Berón
Sofía Fernández-Ciganda
María José Benítez-Galeano
Nélida Rodríguez-Osorio
Luciana Silva-Flannery
Yisell Perdomo
Andrés Cabrera
Rodrigo Puentes
Rodney Colina
Jana M. Ritter
Matías Castells
author_sort Federico Giannitti
collection DOAJ
description <i>Bovine polyomavirus-1</i> (BoPyV-1, <i>Epsilonpolyomavirus bovis</i>) 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 <i>Human polyomavirus-1</i>-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.
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spelling doaj.art-494330c0d2dd4bab91168d84be2b53ba2023-11-23T19:28:35ZengMDPI AGViruses1999-49152022-09-01149204210.3390/v14092042<i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of HumansFederico Giannitti0Caroline da Silva Silveira1Hannah Bullock2Marina Berón3Sofía Fernández-Ciganda4María José Benítez-Galeano5Nélida Rodríguez-Osorio6Luciana Silva-Flannery7Yisell Perdomo8Andrés Cabrera9Rodrigo Puentes10Rodney Colina11Jana M. Ritter12Matías Castells13Plataforma de Investigación en Salud Animal, Instituto Nacional de Investigación Agropecuaria (INIA), Estación Experimental La Estanzuela, Colonia 70006, UruguayPlataforma de Investigación en Salud Animal, Instituto Nacional de Investigación Agropecuaria (INIA), Estación Experimental La Estanzuela, Colonia 70006, UruguaySynergy America Inc., Atlanta, GA 30329, USAPlataforma de Investigación en Salud Animal, Instituto Nacional de Investigación Agropecuaria (INIA), Estación Experimental La Estanzuela, Colonia 70006, UruguayPlataforma de Investigación en Salud Animal, Instituto Nacional de Investigación Agropecuaria (INIA), Estación Experimental La Estanzuela, Colonia 70006, UruguayUnidad de Genómica y Bioinformática, Departamento de Ciencias Biológicas, Centro Universitario Regional (CENUR) Litoral Norte, Universidad de la República, Salto 50000, UruguayUnidad de Genómica y Bioinformática, Departamento de Ciencias Biológicas, Centro Universitario Regional (CENUR) Litoral Norte, Universidad de la República, Salto 50000, UruguayInfectious Diseases Pathology Branch, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USAPlataforma de Investigación en Salud Animal, Instituto Nacional de Investigación Agropecuaria (INIA), Estación Experimental La Estanzuela, Colonia 70006, UruguayFacultad de Veterinaria, Universidad de la República, Montevideo 13000, UruguayFacultad de Veterinaria, Universidad de la República, Montevideo 13000, UruguayLaboratorio de Virología Molecular, Departamento de Ciencias Biológicas, Centro Universitario Regional (CENUR) Litoral Norte, Universidad de la República, Salto 50000, UruguayInfectious Diseases Pathology Branch, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USALaboratorio de Virología Molecular, Departamento de Ciencias Biológicas, Centro Universitario Regional (CENUR) Litoral Norte, Universidad de la República, Salto 50000, Uruguay<i>Bovine polyomavirus-1</i> (BoPyV-1, <i>Epsilonpolyomavirus bovis</i>) 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 <i>Human polyomavirus-1</i>-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.https://www.mdpi.com/1999-4915/14/9/2042abortioncattlepathologyreproductive diseasesviral diseasesemerging diseases
spellingShingle Federico Giannitti
Caroline da Silva Silveira
Hannah Bullock
Marina Berón
Sofía Fernández-Ciganda
María José Benítez-Galeano
Nélida Rodríguez-Osorio
Luciana Silva-Flannery
Yisell Perdomo
Andrés Cabrera
Rodrigo Puentes
Rodney Colina
Jana M. Ritter
Matías Castells
<i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans
Viruses
abortion
cattle
pathology
reproductive diseases
viral diseases
emerging diseases
title <i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans
title_full <i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans
title_fullStr <i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans
title_full_unstemmed <i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans
title_short <i>Bovine Polyomavirus-1</i> (<i>Epsilonpolyomavirus bovis</i>): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans
title_sort i bovine polyomavirus 1 i i epsilonpolyomavirus bovis i an emerging fetal pathogen of cattle that causes renal lesions resembling polyomavirus associated nephropathy of humans
topic abortion
cattle
pathology
reproductive diseases
viral diseases
emerging diseases
url https://www.mdpi.com/1999-4915/14/9/2042
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