title: Molecular characterization of a putative antiretroviral transcriptional factor, OTK18.
abstract: Elucidation of the factors involved in host defense against human immunodeficiency viral infection remains pivotal if viral control may be achieved. Toward these ends, we investigated the function of a putative antiretroviral factor, OTK18, isolated by differential display of mRNA from HIV type 1-infected primary human monocyte-derived macrophages. Molecular and immunohistochemical analyses showed that the OTK18 nucleotide sequence contains 13 adjacent C(2)H(2)-type zinc finger motifs, a Krüppel-associated box, and is localized to both cytosol and nucleus. Mutational analyses revealed that both the Krüppel-associated box and zinc finger regions of OTK18 are responsible for the transcriptional suppressive activities of this gene. OTK18 was copiously expressed in macrophages following HIV type I infection and diminished progeny virion production. A mechanism for this antiretroviral activity was by suppression of HIV type 1 Tat-induced viral long terminal repeat promoter activity. Our findings suggest that one possible function of OTK18 is as a HIV type 1-inducible transcriptional suppressor.
authors.affiliation: Department of Pathology and Microbiology, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Carlson
authors.forename: Gary
authors.initials: G
authors.lastname: Leisman
authors.forename: Jenae
authors.initials: J
authors.lastname: Limoges
authors.forename: Garrett D
authors.initials: GD
authors.lastname: Pohlman
authors.forename: Masahide
authors.initials: M
authors.lastname: Horiba
authors.forename: James
authors.initials: J
authors.lastname: Buescher
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Ikezu
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020079:Terminal Repeat Sequences / Q000276:immunology; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014779:Virus Replication / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C104178:ZNF175 protein, human; C422407:ZNF350 protein, human