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Molecular Characterization of a Putative Antiretroviral Transcriptional Factor, OTK18¹

Kimberly A. Carlson^*, Gary Leisman^*, Jenae Limoges, Garrett D. Pohlman^*, Masahide Horiba^*, James Buescher^*, Howard E. Gendelman^2,*, and Tsuneya Ikezu^2,*

Departments of ^* Pathology and Microbiology and Internal Medicine, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198

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 C₂H₂-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 suppresser.

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The JI 2004 172: 1-2. [Full Text]  

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