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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviruses, Human / genetics
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Amino Acid Sequence
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Anti-HIV Agents / chemistry*
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Anti-HIV Agents / metabolism
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Anti-HIV Agents / pharmacology
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Cell Line
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Cells, Cultured
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Cytosol / chemistry
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Cytosol / metabolism
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Down-Regulation / immunology
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Gene Expression Regulation, Viral / physiology
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HIV-1 / immunology
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Humans
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Macrophages / metabolism
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Macrophages / virology
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Molecular Sequence Data
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Monocytes / metabolism
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Monocytes / virology
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / immunology
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Repressor Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Terminal Repeat Sequences / immunology
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Transcription Factors / chemistry*
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription Factors / physiology
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Virus Replication / immunology
Substances
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Anti-HIV Agents
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DNA-Binding Proteins
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Nuclear Proteins
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Repressor Proteins
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Transcription Factors
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ZNF175 protein, human
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ZNF350 protein, human