A U5 repressor of reverse transcription is required for optimal HIV-1 infectivity and replication
Identifieur interne : 000F19 ( Pmc/Corpus ); précédent : 000F18; suivant : 000F20A U5 repressor of reverse transcription is required for optimal HIV-1 infectivity and replication
Auteurs : Luke Meredith ; Céline Ducloux ; Catherine Isel ; Roland Marquet ; David HarrichSource :
- Retrovirology [ 1742-4690 ] ; 2009.
Url:
DOI: 10.1186/1742-4690-6-S2-O14
PubMed: NONE
PubMed Central: 2766968
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A U5 repressor of reverse transcription is required for optimal HIV-1 infectivity and replication</title><author><name sortKey="Meredith, Luke" sort="Meredith, Luke" uniqKey="Meredith L" first="Luke" last="Meredith">Luke Meredith</name><affiliation><nlm:aff id="I1">Griffith Medical Research College, a joint program of Griffith University and the Queensland Institute of Medical Research, QIMR, Herston, QLD, Australia, 4006</nlm:aff></affiliation><affiliation><nlm:aff id="I2">Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office, Brisbane 4029, Qld, Australia</nlm:aff></affiliation></author><author><name sortKey="Ducloux, Celine" sort="Ducloux, Celine" uniqKey="Ducloux C" first="Céline" last="Ducloux">Céline Ducloux</name><affiliation><nlm:aff id="I3">Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg cedex, France</nlm:aff></affiliation></author><author><name sortKey="Isel, Catherine" sort="Isel, Catherine" uniqKey="Isel C" first="Catherine" last="Isel">Catherine Isel</name><affiliation><nlm:aff id="I3">Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg cedex, France</nlm:aff></affiliation></author><author><name sortKey="Marquet, Roland" sort="Marquet, Roland" uniqKey="Marquet R" first="Roland" last="Marquet">Roland Marquet</name><affiliation><nlm:aff id="I3">Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg cedex, France</nlm:aff></affiliation></author><author><name sortKey="Harrich, David" sort="Harrich, David" uniqKey="Harrich D" first="David" last="Harrich">David Harrich</name><affiliation><nlm:aff id="I1">Griffith Medical Research College, a joint program of Griffith University and the Queensland Institute of Medical Research, QIMR, Herston, QLD, Australia, 4006</nlm:aff></affiliation><affiliation><nlm:aff id="I2">Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office, Brisbane 4029, Qld, Australia</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">2766968</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766968</idno><idno type="RBID">PMC:2766968</idno><idno type="doi">10.1186/1742-4690-6-S2-O14</idno><idno type="pmid">NONE</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000F19</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F19</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A U5 repressor of reverse transcription is required for optimal HIV-1 infectivity and replication</title><author><name sortKey="Meredith, Luke" sort="Meredith, Luke" uniqKey="Meredith L" first="Luke" last="Meredith">Luke Meredith</name><affiliation><nlm:aff id="I1">Griffith Medical Research College, a joint program of Griffith University and the Queensland Institute of Medical Research, QIMR, Herston, QLD, Australia, 4006</nlm:aff></affiliation><affiliation><nlm:aff id="I2">Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office, Brisbane 4029, Qld, Australia</nlm:aff></affiliation></author><author><name sortKey="Ducloux, Celine" sort="Ducloux, Celine" uniqKey="Ducloux C" first="Céline" last="Ducloux">Céline Ducloux</name><affiliation><nlm:aff id="I3">Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg cedex, France</nlm:aff></affiliation></author><author><name sortKey="Isel, Catherine" sort="Isel, Catherine" uniqKey="Isel C" first="Catherine" last="Isel">Catherine Isel</name><affiliation><nlm:aff id="I3">Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg cedex, France</nlm:aff></affiliation></author><author><name sortKey="Marquet, Roland" sort="Marquet, Roland" uniqKey="Marquet R" first="Roland" last="Marquet">Roland Marquet</name><affiliation><nlm:aff id="I3">Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg cedex, France</nlm:aff></affiliation></author><author><name sortKey="Harrich, David" sort="Harrich, David" uniqKey="Harrich D" first="David" last="Harrich">David Harrich</name><affiliation><nlm:aff id="I1">Griffith Medical Research College, a joint program of Griffith University and the Queensland Institute of Medical Research, QIMR, Herston, QLD, Australia, 4006</nlm:aff></affiliation><affiliation><nlm:aff id="I2">Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office, Brisbane 4029, Qld, Australia</nlm:aff></affiliation></author></analytic><series><title level="j">Retrovirology</title><idno type="eISSN">1742-4690</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader></TEI><pmc article-type="abstract"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Retrovirology</journal-id><journal-title>Retrovirology</journal-title><issn pub-type="epub">1742-4690</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">2766968</article-id><article-id pub-id-type="publisher-id">1742-4690-6-S2-O14</article-id><article-id pub-id-type="doi">10.1186/1742-4690-6-S2-O14</article-id><article-categories><subj-group subj-group-type="heading"><subject>Oral Presentation</subject></subj-group></article-categories><title-group><article-title>A U5 repressor of reverse transcription is required for optimal HIV-1 infectivity and replication</article-title></title-group><contrib-group><contrib id="A1" contrib-type="author"><name><surname>Meredith</surname><given-names>Luke</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref></contrib><contrib id="A2" contrib-type="author"><name><surname>Ducloux</surname><given-names>Céline</given-names></name><xref ref-type="aff" rid="I3">3</xref></contrib><contrib id="A3" contrib-type="author"><name><surname>Isel</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="I3">3</xref></contrib><contrib id="A4" contrib-type="author"><name><surname>Marquet</surname><given-names>Roland</given-names></name><xref ref-type="aff" rid="I3">3</xref></contrib><contrib id="A5" corresp="yes" contrib-type="author"><name><surname>Harrich</surname><given-names>David</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref></contrib></contrib-group><aff id="I1"><label>1</label>Griffith Medical Research College, a joint program of Griffith University and the Queensland Institute of Medical Research, QIMR, Herston, QLD, Australia, 4006</aff><aff id="I2"><label>2</label>Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office, Brisbane 4029, Qld, Australia</aff><aff id="I3"><label>3</label>Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg cedex, France</aff><pub-date pub-type="collection"><year>2009</year></pub-date><pub-date pub-type="epub"><day>24</day><month>9</month><year>2009</year></pub-date><volume>6</volume><issue>Suppl 2</issue><supplement><named-content content-type="supplement-title">Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</named-content><ext-link ext-link-type="uri" xlink:href="http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf">http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</ext-link></supplement><fpage>O14</fpage><lpage>O14</lpage><ext-link ext-link-type="uri" xlink:href="http://www.retrovirology.com/content/6/S2/O14"></ext-link><permissions><copyright-statement>Copyright © 2009 Meredith et al; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2009</copyright-year><copyright-holder>Meredith et al; licensee BioMed Central Ltd.</copyright-holder></permissions><conference><conf-date>21–23 September 2009</conf-date><conf-name>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</conf-name><conf-loc>Montpellier, France</conf-loc></conference></article-meta></front><body><p>Here we provide strong evidence that a highly conserved stem loop structure in the U5 region of the HIV-1 RNA leader harbours a repressor of reverse transcription (RRT). We showed that two sequences in U5, at +143-145 and +151-153, are essential for RRT function. Mutation of either site strongly and unexpectedly increased endogenous reverse transcription, and cell infection assays showed that both mutations dramatically increased negative strand strong stop DNA synthesis. Early, late, 1-LTR and 2-LTR reverse transcription products were present proportionally, indicating that the downstream reverse transcription events were not affected. <italic>In vitro </italic>structural probing of the wild type and mutant RNA revealed an unexpected destabilization effect of the mutations on the whole U5 stem loop, which would explain the loss of regulation of reverse transcription. This functional effect was not observed <italic>in vitro</italic>, where, in the absence of viral proteins other than RT and cellular factors, all RNA performed similarly. These U5 mutations decreased virus replication in Jurkat and primary T-cells, which could be attributed to a marked defect in viral integration. Analysis of 1-LTR and 2-LTR circular DNA isolated from infected cells revealed that substantial deletions were present, indicating that the viral DNA was degraded by cellular nucleases. Together, our experiments suggest that regulated reverse transcription initiation is essential to allow synthesis of the viral DNA in a cellular environment that supports the assembly of a functional HIV-1 pre-integration complex, which also protects the proviral DNA from cellular degradation processes.</p></body></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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