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dc.contributor.authorM. Marshall, Heather
dc.contributor.authorRonen, Keshet
dc.contributor.authorBerry, Charles
dc.contributor.authorLlano, Manuel
dc.contributor.authorSutherland, Heidi
dc.contributor.authorSaenz, Dyana
dc.contributor.authorBickmore, Wendy
dc.contributor.authorPoeschla, Eric
dc.contributor.authorD. Bushman, Frederic
dc.date.accessioned2018-01-12T00:25:02Z
dc.date.available2018-01-12T00:25:02Z
dc.date.issued2007
dc.date.modified2014-05-26T00:59:52Z
dc.identifier.issn19326203
dc.identifier.doi10.1371/journal.pone.0001340
dc.identifier.urihttp://hdl.handle.net/10072/59357
dc.description.abstractBackground To replicate, lentiviruses such as HIV must integrate DNA copies of their RNA genomes into host cell chromosomes. Lentiviral integration is favored in active transcription units, which allows efficient viral gene expression after integration, but the mechanisms directing integration targeting are incompletely understood. A cellular protein, PSIP1/LEDGF/p75, binds tightly to the lentiviral-encoded integrase protein (IN), and has been reported to be important for HIV infectivity and integration targeting. Methodology Here we report studies of lentiviral integration targeting in 1) human cells with intensified RNAi knockdowns of PSIP1/LEDGF/p75, and 2) murine cells with homozygous gene trap mutations in the PSIP1/LEDGF/p75 locus. Infections with vectors derived from equine infections anemia virus (EIAV) and HIV were compared. Integration acceptor sites were analyzed by DNA bar coding and pyrosequencing. Conclusions/Significance In both PSIP1/LEDGF/p75-depleted cell lines, reductions were seen in lentiviral infectivity compared to controls. For the human cells, integration was reduced in transcription units in the knockdowns, and this reduction was greater than in our previous studies of human cells less completely depleted for PSIP1/LEDGF/p75. For the homozygous mutant mouse cells, similar reductions in integration in transcription units were seen, paralleling a previous study of a different mutant mouse line. Integration did not become random, however-integration in transcription units in both cell types was still favored, though to a reduced degree. New trends also appeared, including favored integration near CpG islands. In addition, we carried out a bioinformatic study of 15 HIV integration site data sets in different cell types, which showed that the frequency of integration in transcription units was correlated with the cell-type specific levels of PSIP1/LEDGF/p75 expression.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome1340-1
dc.relation.ispartofpagetoe1340-13
dc.relation.ispartofissue12
dc.relation.ispartofjournalPloS One
dc.relation.ispartofvolume2
dc.rights.retentionY
dc.subject.fieldofresearchVirology
dc.subject.fieldofresearchcode060506
dc.titleRole of PSIP1/LEDGF/p75 in Lentiviral Infectivity and Integration Targeting
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.description.versionPublished
gro.rights.copyright© 2007 Marshall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorSutherland, Heidi


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