Molecular characterization of a putative antiretroviral transcriptional factor, OTK18
Title | Molecular characterization of a putative antiretroviral transcriptional factor, OTK18 |
Publication Type | Journal Article |
Year of Publication | 2004 |
Authors | Carlson, KA, Leisman, G, Limoges, J, Pohlman, GD, Horiba, M, Buescher, J, Gendelman, HE, Ikezu, T |
Journal | Journal of Immunology (Baltimore, Md.: 1950) |
Volume | 172 |
Issue | 1 |
Pagination | 381-91 |
Date Published | 01/2004 |
Keywords | Adenoviruses, 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 |
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. |
URL | http://www.ncbi.nlm.nih.gov/pubmed/14688346 |