Source:http://linkedlifedata.com/resource/pubmed/id/16227231
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 11
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pubmed:dateCreated |
2005-10-17
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pubmed:abstractText |
The antiviral efficacy of ten antisense phosphorodiamidate morpholino oligomers (PMOs) directed against Equine arteritis virus (EAV), a nidovirus belonging to the family Arteriviridae, was evaluated in mammalian (Vero-E6) cells. Peptide-conjugated PMOs (P-PMOs) supplied in cell culture medium at micromolar concentrations were efficiently taken up by Vero-E6 cells and were minimally cytotoxic. The P-PMOs were designed to base pair to RNA sequences involved in different aspects of EAV amplification: genome replication, subgenomic mRNA synthesis, and translation of genome and subgenomic mRNAs. A novel recombinant EAV, expressing green fluorescent protein as part of its replicase polyproteins, was used to facilitate drug screening. A moderate reduction of EAV amplification was observed with relatively high concentrations of P-PMOs designed to anneal to the 3'-terminal regions of the viral genome or antigenome. To determine if the synthesis of subgenomic mRNAs could be specifically reduced, transcription-regulating sequences essential for their production, but not for the production of genomic RNA, were targeted, but these P-PMOs were found to be ineffective at transcription interference. In contrast, all four P-PMOs designed to base pair with targets in the genomic 5' untranslated region markedly reduced virus amplification in a sequence-specific and dose-responsive manner. At concentrations in the low micromolar range, some of the P-PMOs tested completely inhibited virus amplification. In vitro translation assays showed that these P-PMOs were potent inhibitors of translation. The data suggest that these compounds could be useful as reagents for exploring the molecular mechanics of nidovirus translation and have anti-EAV potential at relatively low concentrations.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-1317
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
86
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3081-90
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16227231-Animals,
pubmed-meshheading:16227231-Arteritis Virus, Equine,
pubmed-meshheading:16227231-Cell Line,
pubmed-meshheading:16227231-Cercopithecus aethiops,
pubmed-meshheading:16227231-Gene Amplification,
pubmed-meshheading:16227231-Morpholines,
pubmed-meshheading:16227231-Morpholinos,
pubmed-meshheading:16227231-Nucleic Acid Conformation,
pubmed-meshheading:16227231-Oligonucleotides, Antisense,
pubmed-meshheading:16227231-Vero Cells,
pubmed-meshheading:16227231-Virus Replication
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pubmed:year |
2005
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pubmed:articleTitle |
Antiviral activity of morpholino oligomers designed to block various aspects of Equine arteritis virus amplification in cell culture.
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pubmed:affiliation |
Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, LUMC P4-26, PO Box 9600, 2300 RC Leiden, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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