Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.

Merkel Cell Polyomavirus (MCPyV) genomes are clonally integrated in tumor tissues of approximately 85% of all Merkel cell carcinoma (MCC) cases, a highly aggressive tumor of the skin which predominantly afflicts elderly and immunosuppressed patients. All integrated viral genomes recovered from MCC t...

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Autores principales: Friederike Neumann, Sophie Borchert, Claudia Schmidt, Rudolph Reimer, Heinrich Hohenberg, Nicole Fischer, Adam Grundhoff
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/0c47849d92c14ff680859362480d2774
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spelling oai:doaj.org-article:0c47849d92c14ff680859362480d27742021-11-18T07:31:32ZReplication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.1932-620310.1371/journal.pone.0029112https://doaj.org/article/0c47849d92c14ff680859362480d27742011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22216177/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Merkel Cell Polyomavirus (MCPyV) genomes are clonally integrated in tumor tissues of approximately 85% of all Merkel cell carcinoma (MCC) cases, a highly aggressive tumor of the skin which predominantly afflicts elderly and immunosuppressed patients. All integrated viral genomes recovered from MCC tissue or MCC cell lines harbor signature mutations in the early gene transcript encoding for the large T-Antigen (LT-Ag). These mutations selectively abrogate the ability of LT-Ag to support viral replication while still maintaining its Rb-binding activity, suggesting a continuous requirement for LT-Ag mediated cell cycle deregulation during MCC pathogenesis. To gain a better understanding of MCPyV biology, in vitro MCPyV replication systems are required. We have generated a synthetic MCPyV genomic clone (MCVSyn) based on the consensus sequence of MCC-derived sequences deposited in the NCBI database. Here, we demonstrate that transfection of recircularized MCVSyn DNA into some human cell lines recapitulates efficient replication of the viral genome, early and late gene expression together with virus particle formation. However, serial transmission of infectious virus was not observed. This in vitro culturing system allows the study of viral replication and will facilitate the molecular dissection of important aspects of the MCPyV lifecycle.Friederike NeumannSophie BorchertClaudia SchmidtRudolph ReimerHeinrich HohenbergNicole FischerAdam GrundhoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29112 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Friederike Neumann
Sophie Borchert
Claudia Schmidt
Rudolph Reimer
Heinrich Hohenberg
Nicole Fischer
Adam Grundhoff
Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.
description Merkel Cell Polyomavirus (MCPyV) genomes are clonally integrated in tumor tissues of approximately 85% of all Merkel cell carcinoma (MCC) cases, a highly aggressive tumor of the skin which predominantly afflicts elderly and immunosuppressed patients. All integrated viral genomes recovered from MCC tissue or MCC cell lines harbor signature mutations in the early gene transcript encoding for the large T-Antigen (LT-Ag). These mutations selectively abrogate the ability of LT-Ag to support viral replication while still maintaining its Rb-binding activity, suggesting a continuous requirement for LT-Ag mediated cell cycle deregulation during MCC pathogenesis. To gain a better understanding of MCPyV biology, in vitro MCPyV replication systems are required. We have generated a synthetic MCPyV genomic clone (MCVSyn) based on the consensus sequence of MCC-derived sequences deposited in the NCBI database. Here, we demonstrate that transfection of recircularized MCVSyn DNA into some human cell lines recapitulates efficient replication of the viral genome, early and late gene expression together with virus particle formation. However, serial transmission of infectious virus was not observed. This in vitro culturing system allows the study of viral replication and will facilitate the molecular dissection of important aspects of the MCPyV lifecycle.
format article
author Friederike Neumann
Sophie Borchert
Claudia Schmidt
Rudolph Reimer
Heinrich Hohenberg
Nicole Fischer
Adam Grundhoff
author_facet Friederike Neumann
Sophie Borchert
Claudia Schmidt
Rudolph Reimer
Heinrich Hohenberg
Nicole Fischer
Adam Grundhoff
author_sort Friederike Neumann
title Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.
title_short Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.
title_full Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.
title_fullStr Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.
title_full_unstemmed Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.
title_sort replication, gene expression and particle production by a consensus merkel cell polyomavirus (mcpyv) genome.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/0c47849d92c14ff680859362480d2774
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