Molecular characterization of a putative antiretroviral transcriptional factor, OTK18.
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.
Carlson
Kimberly A
KA
Department of Pathology and Microbiology, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Leisman
Gary
G
Limoges
Jenae
J
Pohlman
Garrett D
GD
Horiba
Masahide
M
Buescher
James
J
Gendelman
Howard E
HE
Ikezu
Tsuneya
T
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
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