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Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo
There is increasing evidence for a connection between DNA replication and the expression of adjacent genes. Therefore, this study addressed the question of whether a herpesvirus origin of replication can be used to activate or increase the expression of adjacent genes. Cell lines carrying an episoma...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369935/ https://www.ncbi.nlm.nih.gov/pubmed/22685399 http://dx.doi.org/10.1371/journal.ppat.1002728 |
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author | Mohr, Hermine Mohr, Christian A. Schneider, Marlon R. Scrivano, Laura Adler, Barbara Kraner-Schreiber, Simone Schnieke, Angelika Dahlhoff, Maik Wolf, Eckhard Koszinowski, Ulrich H. Ruzsics, Zsolt |
author_facet | Mohr, Hermine Mohr, Christian A. Schneider, Marlon R. Scrivano, Laura Adler, Barbara Kraner-Schreiber, Simone Schnieke, Angelika Dahlhoff, Maik Wolf, Eckhard Koszinowski, Ulrich H. Ruzsics, Zsolt |
author_sort | Mohr, Hermine |
collection | PubMed |
description | There is increasing evidence for a connection between DNA replication and the expression of adjacent genes. Therefore, this study addressed the question of whether a herpesvirus origin of replication can be used to activate or increase the expression of adjacent genes. Cell lines carrying an episomal vector, in which reporter genes are linked to the murine cytomegalovirus (MCMV) origin of lytic replication (oriLyt), were constructed. Reporter gene expression was silenced by a histone-deacetylase-dependent mechanism, but was resolved upon lytic infection with MCMV. Replication of the episome was observed subsequent to infection, leading to the induction of gene expression by more than 1000-fold. oriLyt-based regulation thus provided a unique opportunity for virus-induced conditional gene expression without the need for an additional induction mechanism. This principle was exploited to show effective late trans-complementation of the toxic viral protein M50 and the glycoprotein gO of MCMV. Moreover, the application of this principle for intracellular immunization against herpesvirus infection was demonstrated. The results of the present study show that viral infection specifically activated the expression of a dominant-negative transgene, which inhibited viral growth. This conditional system was operative in explant cultures of transgenic mice, but not in vivo. Several applications are discussed. |
format | Online Article Text |
id | pubmed-3369935 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33699352012-06-08 Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo Mohr, Hermine Mohr, Christian A. Schneider, Marlon R. Scrivano, Laura Adler, Barbara Kraner-Schreiber, Simone Schnieke, Angelika Dahlhoff, Maik Wolf, Eckhard Koszinowski, Ulrich H. Ruzsics, Zsolt PLoS Pathog Research Article There is increasing evidence for a connection between DNA replication and the expression of adjacent genes. Therefore, this study addressed the question of whether a herpesvirus origin of replication can be used to activate or increase the expression of adjacent genes. Cell lines carrying an episomal vector, in which reporter genes are linked to the murine cytomegalovirus (MCMV) origin of lytic replication (oriLyt), were constructed. Reporter gene expression was silenced by a histone-deacetylase-dependent mechanism, but was resolved upon lytic infection with MCMV. Replication of the episome was observed subsequent to infection, leading to the induction of gene expression by more than 1000-fold. oriLyt-based regulation thus provided a unique opportunity for virus-induced conditional gene expression without the need for an additional induction mechanism. This principle was exploited to show effective late trans-complementation of the toxic viral protein M50 and the glycoprotein gO of MCMV. Moreover, the application of this principle for intracellular immunization against herpesvirus infection was demonstrated. The results of the present study show that viral infection specifically activated the expression of a dominant-negative transgene, which inhibited viral growth. This conditional system was operative in explant cultures of transgenic mice, but not in vivo. Several applications are discussed. Public Library of Science 2012-06-07 /pmc/articles/PMC3369935/ /pubmed/22685399 http://dx.doi.org/10.1371/journal.ppat.1002728 Text en Mohr et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mohr, Hermine Mohr, Christian A. Schneider, Marlon R. Scrivano, Laura Adler, Barbara Kraner-Schreiber, Simone Schnieke, Angelika Dahlhoff, Maik Wolf, Eckhard Koszinowski, Ulrich H. Ruzsics, Zsolt Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo |
title | Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo
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title_full | Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo
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title_fullStr | Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo
|
title_full_unstemmed | Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo
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title_short | Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo
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title_sort | cytomegalovirus replicon-based regulation of gene expression in vitro and in vivo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369935/ https://www.ncbi.nlm.nih.gov/pubmed/22685399 http://dx.doi.org/10.1371/journal.ppat.1002728 |
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