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Expression and replication of virus-like circular DNA in human cells

The consumption of bovine milk and meat is considered a risk factor for colon- and breast cancer formation, and milk consumption has also been implicated in an increased risk for developing Multiple Sclerosis (MS). A number of highly related virus-like DNAs have been recently isolated from bovine mi...

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Autores principales: Eilebrecht, Sebastian, Hotz-Wagenblatt, Agnes, Sarachaga, Victor, Burk, Amelie, Falida, Konstantina, Chakraborty, Deblina, Nikitina, Ekaterina, Tessmer, Claudia, Whitley, Corinna, Sauerland, Charlotte, Gunst, Karin, Grewe, Imke, Bund, Timo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809378/
https://www.ncbi.nlm.nih.gov/pubmed/29434270
http://dx.doi.org/10.1038/s41598-018-21317-w
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author Eilebrecht, Sebastian
Hotz-Wagenblatt, Agnes
Sarachaga, Victor
Burk, Amelie
Falida, Konstantina
Chakraborty, Deblina
Nikitina, Ekaterina
Tessmer, Claudia
Whitley, Corinna
Sauerland, Charlotte
Gunst, Karin
Grewe, Imke
Bund, Timo
author_facet Eilebrecht, Sebastian
Hotz-Wagenblatt, Agnes
Sarachaga, Victor
Burk, Amelie
Falida, Konstantina
Chakraborty, Deblina
Nikitina, Ekaterina
Tessmer, Claudia
Whitley, Corinna
Sauerland, Charlotte
Gunst, Karin
Grewe, Imke
Bund, Timo
author_sort Eilebrecht, Sebastian
collection PubMed
description The consumption of bovine milk and meat is considered a risk factor for colon- and breast cancer formation, and milk consumption has also been implicated in an increased risk for developing Multiple Sclerosis (MS). A number of highly related virus-like DNAs have been recently isolated from bovine milk and sera and from a brain sample of a MS patient. As a genetic activity of these Acinetobacter-related bovine milk and meat factors (BMMFs) is unknown in eukaryotes, we analyzed their expression and replication potential in human HEK293TT cells. While all analyzed BMMFs show transcriptional activity, the MS brain isolate MSBI1.176, sharing homology with a transmissible spongiform encephalopathy-associated DNA molecule, is transcribed at highest levels. We show expression of a replication-associated protein (Rep), which is highly conserved among all BMMFs, and serological tests indicate a human anti-Rep immune response. While the cow milk isolate CMI1.252 is replication-competent in HEK293TT cells, replication of MSBI1.176 is complemented by CMI1.252, pointing at an interplay during the establishment of persistence in human cells. Transcriptome profiling upon BMMF expression identified host cellular gene expression changes related to cell cycle progression and cell viability control, indicating potential pathways for a pathogenic involvement of BMMFs.
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spelling pubmed-58093782018-02-15 Expression and replication of virus-like circular DNA in human cells Eilebrecht, Sebastian Hotz-Wagenblatt, Agnes Sarachaga, Victor Burk, Amelie Falida, Konstantina Chakraborty, Deblina Nikitina, Ekaterina Tessmer, Claudia Whitley, Corinna Sauerland, Charlotte Gunst, Karin Grewe, Imke Bund, Timo Sci Rep Article The consumption of bovine milk and meat is considered a risk factor for colon- and breast cancer formation, and milk consumption has also been implicated in an increased risk for developing Multiple Sclerosis (MS). A number of highly related virus-like DNAs have been recently isolated from bovine milk and sera and from a brain sample of a MS patient. As a genetic activity of these Acinetobacter-related bovine milk and meat factors (BMMFs) is unknown in eukaryotes, we analyzed their expression and replication potential in human HEK293TT cells. While all analyzed BMMFs show transcriptional activity, the MS brain isolate MSBI1.176, sharing homology with a transmissible spongiform encephalopathy-associated DNA molecule, is transcribed at highest levels. We show expression of a replication-associated protein (Rep), which is highly conserved among all BMMFs, and serological tests indicate a human anti-Rep immune response. While the cow milk isolate CMI1.252 is replication-competent in HEK293TT cells, replication of MSBI1.176 is complemented by CMI1.252, pointing at an interplay during the establishment of persistence in human cells. Transcriptome profiling upon BMMF expression identified host cellular gene expression changes related to cell cycle progression and cell viability control, indicating potential pathways for a pathogenic involvement of BMMFs. Nature Publishing Group UK 2018-02-12 /pmc/articles/PMC5809378/ /pubmed/29434270 http://dx.doi.org/10.1038/s41598-018-21317-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Eilebrecht, Sebastian
Hotz-Wagenblatt, Agnes
Sarachaga, Victor
Burk, Amelie
Falida, Konstantina
Chakraborty, Deblina
Nikitina, Ekaterina
Tessmer, Claudia
Whitley, Corinna
Sauerland, Charlotte
Gunst, Karin
Grewe, Imke
Bund, Timo
Expression and replication of virus-like circular DNA in human cells
title Expression and replication of virus-like circular DNA in human cells
title_full Expression and replication of virus-like circular DNA in human cells
title_fullStr Expression and replication of virus-like circular DNA in human cells
title_full_unstemmed Expression and replication of virus-like circular DNA in human cells
title_short Expression and replication of virus-like circular DNA in human cells
title_sort expression and replication of virus-like circular dna in human cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809378/
https://www.ncbi.nlm.nih.gov/pubmed/29434270
http://dx.doi.org/10.1038/s41598-018-21317-w
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