title: OTK18, a zinc-finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions.
abstract: It has previously been shown by our laboratory that OTK18, a human immunodeficiency virus (HIV)-inducible zinc-finger protein, reduces progeny-virion production in infected human macrophages. OTK18 antiviral activity is mediated through suppression of Tat-induced HIV-1 long terminal repeat (LTR) promoter activity. Through the use of LTR-scanning mutant vectors, the specific regions responsible for OTK18-mediated LTR suppression have been defined. Two different LTR regions were identified as potential OTK18-binding sites by an enhanced DNA-transcription factor ELISA system; the negative-regulatory element (NRE) at -255/-238 and the Ets-binding site (EBS) at -150/-139 in the LTR. In addition, deletion of the EBS in the LTR blocked OTK18-mediated LTR suppression. These data indicate that OTK18 suppresses LTR activity through two distinct regulatory elements. Spontaneous mutations in these regions might enable HIV-1 to escape from OTK18 antiretroviral activity in human macrophages.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.|Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Masahide
authors.initials: M
authors.lastname: Horiba
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.|Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Lindsey B
authors.initials: LB
authors.lastname: Martinez
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.|Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Buescher
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.|Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Shinji
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Jenae
authors.initials: J
authors.lastname: Limoges
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583-0905, USA.
authors.forename: Yunquan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583-0905, USA.
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.|Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Ikezu
mesh_terms: D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D016325:HIV Long Terminal Repeat / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C104178:ZNF175 protein, human