rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2004-1-28
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pubmed:abstractText |
Human immunodeficiency virus type 1 (HIV-1) utilizes a distinctive form of gene regulation as part of its life cycle, termed programmed -1 ribosomal frameshifting, to produce the required ratio of the Gag and Gag-Pol polyproteins. We carried out a sequence comparison of 1,000 HIV-1 sequences at the slippery site (UUUUUUA) and found that the site is invariant, which is somewhat surprising for a virus known for its variability. This prompted us to prepare a series of mutations to examine their effect upon frameshifting and viral infectivity. Among the series of mutations were changes of the HIV-1 slippery site to those effectively utilized by other viruses, because such mutations would be anticipated to have a relatively mild effect upon frameshifting. The results demonstrate that any change to the slippery site reduced frameshifting levels and also dramatically inhibited infectivity. Because ribosomal frameshifting is essential for HIV-1 replication and it is surprisingly resistant to mutation, modulation of HIV-1 frameshifting efficiency potentially represents an important target for the development of novel antiviral therapeutics.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-10419458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-11259192,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-11557856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-11959986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-12239298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-12388684,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-12466532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-1309954,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-1321294,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-1404364,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-1583726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-1883204,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-1986362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-2416054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-2447506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-2846182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-7636469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-7769666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-8510215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-8602510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-8811194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-8982463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-9223476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-9545540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-9630253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747573-9740788
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-538X
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
78
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2082-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:14747573-Anti-HIV Agents,
pubmed-meshheading:14747573-Base Sequence,
pubmed-meshheading:14747573-Cell Line,
pubmed-meshheading:14747573-Frameshifting, Ribosomal,
pubmed-meshheading:14747573-Fusion Proteins, gag-pol,
pubmed-meshheading:14747573-Gene Products, gag,
pubmed-meshheading:14747573-HIV-1,
pubmed-meshheading:14747573-HeLa Cells,
pubmed-meshheading:14747573-Humans,
pubmed-meshheading:14747573-Molecular Sequence Data,
pubmed-meshheading:14747573-Mutation,
pubmed-meshheading:14747573-Virus Replication
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pubmed:year |
2004
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pubmed:articleTitle |
The human immunodeficiency virus type 1 ribosomal frameshifting site is an invariant sequence determinant and an important target for antiviral therapy.
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pubmed:affiliation |
Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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