Molecular characterization of a putative antiretroviral transcriptional factor, OTK18

TitleMolecular characterization of a putative antiretroviral transcriptional factor, OTK18
Publication TypeJournal Article
Year of Publication2004
AuthorsCarlson, KA, Leisman, G, Limoges, J, Pohlman, GD, Horiba, M, Buescher, J, Gendelman, HE, Ikezu, T
JournalJournal of Immunology (Baltimore, Md.: 1950)
Date Published01/2004
KeywordsAdenoviruses, Amino Acid, Cells, Cultured, Cytosol, DNA-Binding Proteins, External, Gene Expression Regulation, Human, Nuclear Proteins, Repressor Proteins, Sequence Alignment, Sequence Homology, Terminal Repeat Sequences, Transcription Factors, Viral

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.