title: Chromatin reassembly factors are involved in transcriptional interference promoting HIV latency.
abstract: The establishment of a stable reservoir of latently infected cells allows HIV to persist in the host. Usually, HIV infection of T cells results in integration of the viral genome, with a preference for regions in the human genome containing active genes, viral expression, and production of new viruses. However, in rare cases T cells become latently infected, and this is presumed to be due to a combination of two factors: integrated viruses are not efficiently transcribed and infected T cells revert to a resting memory state. HIV latency has been associated with provirus integration in regions of constitutive heterochromatin, gene deserts, or very highly expressed genes. We have investigated the transcriptional consequences of latent HIV integration into cellular genes and the involvement of chromatin reassembly factors (CRFs) in the transcriptional interference that a host gene exerts on the integrated cryptic HIV promoter. Chimeric transcripts containing sequences from the host gene and HIV can be detected, having been initiated at promoters of either the cell or the virus. Reactivation of HIV downregulates host gene expression. Cryptic promoters might remain inactive due to the repressive chromatin configuration established by CRFs during transcription elongation. Depletion of CRFs such as Spt6, Chd1, and FACT, or the histone chaperones ASF1a and HIRA, promoted HIV reactivation, concomitantly with chromatin relaxation and a decrease in general RNA polymerase activity. Overall, our results indicate that CRFs play a role in maintaining HIV latency by transcriptional interference when the provirus is integrated into an intron of a highly active gene.
authors.affiliation: Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Baldiri i Reixac 4, E-08028 Barcelona, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Gallastegui
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Millán-Zambrano
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Terme
authors.forename: Sebastián
authors.initials: S
authors.lastname: Chávez
authors.forename: Albert
authors.initials: A
authors.lastname: Jordan
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells; D014158:Transcription, Genetic; D017735:Virus Latency
chemical_list: D002843:Chromatin