title: Position effects influence HIV latency reversal.
abstract: The main obstacle to curing HIV is the presence of latent proviruses in the bodies of infected patients. The partial success of reactivation therapies suggests that the genomic context of integrated proviruses can interfere with treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to map the chromosomal locations of thousands of individual proviruses while tracking their transcriptional activities in an infected cell population. B-HIVE revealed that, in Jurkat cells, the expression of HIV is strongest close to endogenous enhancers. The insertion site also affects the response to latency-reversing agents, because we found that phytohemagglutinin and vorinostat reactivated proviruses inserted at distinct genomic locations. From these results, we propose that combinations of drugs targeting all areas of the genome will be most effective. Overall, our data suggest that the insertion context of HIV is a critical determinant of the viral response to reactivation therapies.
authors.affiliation: Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.|University Pompeu Fabra, Barcelona, Spain.
authors.forename: Heng-Chang
authors.identifier: 0000-0003-2117-7385
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Infection Biology Group, Department of Experimental and Health Sciences, University Pompeu Fabra, Barcelona, Spain.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Martinez
authors.affiliation: Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.|University Pompeu Fabra, Barcelona, Spain.
authors.forename: Eduard
authors.identifier: 0000-0002-0129-0885
authors.initials: E
authors.lastname: Zorita
authors.affiliation: Infection Biology Group, Department of Experimental and Health Sciences, University Pompeu Fabra, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Andreas
authors.identifier: 0000-0003-0620-5317
authors.initials: A
authors.lastname: Meyerhans
authors.affiliation: Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.|University Pompeu Fabra, Barcelona, Spain.
authors.forename: Guillaume J
authors.identifier: 0000-0002-3473-1632
authors.initials: GJ
authors.lastname: Filion
mesh_terms: D005814:Genes, Viral; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D016662:Virus Integration; D017735:Virus Latency