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dc.contributor.authorMeredith, Lukeen_US
dc.contributor.authorDucloux, Célineen_US
dc.contributor.authorIsel, Catherineen_US
dc.contributor.authorMarquet, Rolanden_US
dc.contributor.authorHarrich, Daviden_US
dc.date.accessioned2017-04-24T11:02:03Z
dc.date.available2017-04-24T11:02:03Z
dc.date.issued2009en_US
dc.date.modified2012-09-10T22:25:35Z
dc.identifier.doi10.1186/1742-4690-6-S2-O14en_US
dc.identifier.urihttp://hdl.handle.net/10072/31543
dc.description.abstractHere 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. In vitro 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 in vitro, 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.en_US
dc.description.publicationstatusYesen_US
dc.format.extent138611 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherBioMed Central Ltd.en_US
dc.publisher.placeUnited Kingdomen_US
dc.publisher.urihttp://www.retrovirology.com/supplements/6/S2en_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofconferencenameFrontiers of Retrovirology: Complex retroviruses, retroelements and their hostsen_US
dc.relation.ispartofconferencetitleFrontiers of Retrovirology: Complex retroviruses, retroelements and their hostsen_US
dc.relation.ispartofdatefrom2009-09-21en_US
dc.relation.ispartofdateto2009-09-23en_US
dc.relation.ispartoflocationMontpellier, Franceen_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchMicrobiology not elsewhere classifieden_US
dc.subject.fieldofresearchcode060599en_US
dc.titleA U5 repressor of reverse transcription is required for optimal HIV-1 infectivity and replicationen_US
dc.typeConference outputen_US
dc.type.descriptionE3 - Conference Publications (Extract Paper)en_US
dc.type.codeE - Conference Publicationsen_US
gro.facultyGriffith Health, Griffith University Medical Research Collegeen_US
gro.rights.copyrightCopyright 2009 Meredith et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
gro.date.issued2009
gro.hasfulltextFull Text


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    Contains papers delivered by Griffith authors at national and international conferences.

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