title: RNAP II processivity is a limiting step for HIV-1 transcription independent of orientation to and activity of endogenous neighboring promoters.
abstract: Since HIV-1 has a propensity to integrate into actively expressed genes, transcriptional interference from neighboring host promoters has been proposed to contribute to the establishment and maintenance HIV-1 latency. To gain insights into how endogenous promoters influence HIV-1 transcription we utilized a set of inducible T cell lines and characterized whether there were correlations between expression of endogenous genes, provirus and long terminal repeat architecture. We show that neighboring promoters are active but have minimal impact on HIV-1 transcription, in particular, expression of the endogenous gene did not prevent expression of HIV-1 following induction of latent provirus. We also demonstrate that releasing paused RNAP II by diminishing negative elongation factor (NELF) is sufficient to reactivate transcriptionally repressed HIV-1 provirus regardless of the integration site and orientation of the provirus suggesting that NELF-mediated RNAP II pausing is a common mechanism of maintaining HIV-1 latency.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Graduate Program in Molecular and Translational Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczmarek Michaels
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Wolschendorf
authors.affiliation: University of Rochester Medical Center, Department of Pediatrics, Division of Neonatology, Rochester, NY 14642, USA.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Schiralli Lester
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Malini
authors.initials: M
authors.lastname: Natarajan
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kutsch
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Graduate Program in Molecular and Translational Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: andrew.henderson@bmc.org.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Henderson
mesh_terms: D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C411985:NSMF protein, human; D014157:Transcription Factors; D012319:RNA Polymerase II
keywords: HIV latency; NELF; RNA Polymerase II pausing; Transcription interference