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dc.contributor.authorGray, L.en
dc.contributor.authorCowley, D.en
dc.contributor.authorWelsh, C.en
dc.contributor.authorLu, H.en
dc.contributor.authorBrew, B.en
dc.contributor.authorLewin, S.en
dc.contributor.authorWesselingh, S.en
dc.contributor.authorGorry, P.en
dc.contributor.authorChurchill, M.en
dc.identifier.citationMolecular Psychiatry, 2016; 21(4):574-584en
dc.description.abstractLatency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (CNS) is unknown. Here we show that CNS-derived HIV-1 strains possess polymorphisms within and surrounding the Sp transcription factor motifs in the long terminal repeat (LTR). These polymorphisms result in decreased ability of the transcription factor specificity protein 1 to bind CNS-derived LTRs, reducing the transcriptional activity of CNS-derived viruses. These mutations result in CNS-derived viruses being less responsive to activation by the HDACi panobinostat and romidepsin compared with lymphoid-derived viruses from the same subjects. Our findings suggest that HIV-1 strains residing in the CNS have unique transcriptional regulatory mechanisms, which impact the regulation of latency, the consideration of which is essential for the development of HIV-1 eradication strategies.en
dc.description.statementofresponsibilityLR Gray, D Cowley, C Welsh, HK Lu, BJ Brew, SR Lewin, SL Wesselingh, PR Gorry, and MJ Churchillen
dc.publisherNature Publishing Group: Open Access Hybrid Model Option Ben
dc.rights© 2016 Macmillan Publishers Limited All rights reserveden
dc.subjectCentral Nervous System; Brain; CD4-Positive T-Lymphocytes; Jurkat Cells; Humans; HIV-1; HIV Infections; Hydroxamic Acids; Indoles; Depsipeptides; Cohort Studies; Virus Latency; Terminal Repeat Sequences; Polymorphism, Genetic; Adult; Middle Aged; Male; Transcriptional Activation; Histone Deacetylase Inhibitorsen
dc.titleCNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategiesen
dc.typeJournal articleen
pubs.library.collectionMedicine publicationsen
Appears in Collections:Medicine publications

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