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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1997-2-21
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pubmed:abstractText |
Studies of interferon (IFN)-treated virus-infected animal cells have revealed the 2-5A system (2-5A synthetase/RNase L enzymes) as being responsible for virus inhibition only in the case of picornaviridae. To investigate whether those IFN-induced enzymes could be responsible for inhibition of poxvirus replication, we have generated recombinant vaccinia viruses (VV) containing the corresponding genes (VV-2-5AS and VV-RL, respectively). RNase L produced in cells infected with VV-RL leads to rRNA degradation and inhibition of virus protein synthesis, which correlates with about 92% reduction in virus yields by 48 hr after infection. Combined expression of this enzyme with 2-5A-synthetase further inhibits virus yields. The pattern of rRNA fragments produced by infection with viruses VV-RL and/or VV-2-5AS is the characteristic for activation of the 2-5A pathway by IFN treatment. Combined infection of VV-RL together with vesicular stomatitis virus (VSV) demonstrates this inhibition to be specific for VV and not due to a general effect. Breakdown of rRNA is largely due to the recombinant vector-derived enzyme, since a C-terminal deletion mutant of RNase L is inactive and the extent of rRNA degradation induced by infection with VV-RL is similar in cells treated or not with IFN. Moreover, the anti-VV effects of RNase L is also observed in a cell line lacking the endogenous ds RNA-dependent protein kinase (PKR). Thus, our findings provide direct evidence for antiviral activity of the 2-5A system on poxviruses.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2',5'-Oligoadenylate Synthetase,
http://linkedlifedata.com/resource/pubmed/chemical/2-5A-dependent ribonuclease,
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Endoribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Interferons
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0042-6822
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
227
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
220-8
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pubmed:dateRevised |
2011-6-17
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pubmed:meshHeading |
pubmed-meshheading:9007077-2',5'-Oligoadenylate Synthetase,
pubmed-meshheading:9007077-Animals,
pubmed-meshheading:9007077-Antiviral Agents,
pubmed-meshheading:9007077-Cell Line,
pubmed-meshheading:9007077-Endoribonucleases,
pubmed-meshheading:9007077-Enzyme Induction,
pubmed-meshheading:9007077-Escherichia coli,
pubmed-meshheading:9007077-Humans,
pubmed-meshheading:9007077-Interferons,
pubmed-meshheading:9007077-Mice,
pubmed-meshheading:9007077-Rabbits,
pubmed-meshheading:9007077-Recombination, Genetic,
pubmed-meshheading:9007077-Vaccinia virus,
pubmed-meshheading:9007077-Virus Replication
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pubmed:year |
1997
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pubmed:articleTitle |
Inducible expression of the 2-5A synthetase/RNase L system results in inhibition of vaccinia virus replication.
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pubmed:affiliation |
CSIC, Campus Universidad Autónoma, Madrid, 28049, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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