Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/99315
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dc.contributor.authorGray, L.en
dc.contributor.authorCowley, D.en
dc.contributor.authorCrespan, E.en
dc.contributor.authorWelsh, C.en
dc.contributor.authorMackenzie, C.en
dc.contributor.authorWesselingh, S.en
dc.contributor.authorGorry, P.en
dc.contributor.authorChurchill, M.en
dc.date.issued2013en
dc.identifier.citationAIDS Research and Human Retroviruses, 2013; 29(2):365-370en
dc.identifier.issn0889-2229en
dc.identifier.issn1931-8405en
dc.identifier.urihttp://hdl.handle.net/2440/99315-
dc.description.abstractNew evidence indicates that astrocytes of the central nervous system (CNS) are extensively infected with human immunodeficiency virus type 1 (HIV-1) in vivo. Although no new virus is produced, this nonproductive or restricted infection contributes to the pathogenesis of HIV-associated dementia (HAD) and compromises virus eradication strategies. The HIV-1 long terminal repeat (LTR) plays a critical role in regulating virus production from infected cells. Here, we determined whether LTRs derived from CNS and non-CNS compartments are genetically and functionally distinct and contribute to the restricted nature of astrocyte infection. CNS- and/or non-CNS-derived LTRs (n=82) were cloned from primary HIV-1 viruses isolated from autopsy tissues of seven patients who died with HAD. Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences. Functional analysis showed reduced basal transcriptional activity of CNS-derived LTRs in both astrocytes and T cells compared to that of non-CNS-derived LTRs. However, LTRs were heterogeneous in their responsiveness to activation by Tat. Therefore, using a relatively large, independent panel of primary HIV-1 LTRs derived from clinically well-characterized subjects, we show that LTRs segregate CNS- from non-CNS-derived tissues both genetically and functionally. The reduced basal transcriptional activity of LTRs derived from the CNS may contribute to the restricted HIV-1 infection of astrocytes and latent infection within the CNS. These findings have significance for understanding the molecular basis of HIV-1 persistence within cellular reservoirs of the CNS that need to be considered for strategies aimed at eradicating HIV-1.en
dc.description.statementofresponsibilityLachlan R. Gray, Daniel Cowley, Emma Crespan, Casey Welsh, Charlene Mackenzie, Steve L. Wesselingh, Paul R. Gorry, and Melissa J. Churchill.en
dc.language.isoenen
dc.publisherMary Ann Lieberten
dc.rights© Mary Ann Liebert, Inc.en
dc.subjectAstrocytes; Sequence Analysis, DNAen
dc.titleReduced basal transcriptional activity of central nervous system-derived HIV type 1 long terminal repeatsen
dc.typeJournal articleen
dc.identifier.rmid0030042580en
dc.identifier.doi10.1089/aid.2012.0138en
dc.identifier.pubid115066-
pubs.library.collectionMedicine publicationsen
pubs.library.teamDS08en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Medicine publications

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