Date Published:
01/2004
Publication Type:
Journal Article
Authors:
Secondary:
Journal of Immunology (Baltimore, Md.: 1950)
Volume:
172
Pagination:
381-91
Issue:
1
URL:
https://pubmed.ncbi.nlm.nih.gov/
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:
<p>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.</p>