Molecular Characterization of a Putative Antiretroviral Transcriptional Factor, OTK18

• Published in: The Journal of immunology (1950) 2004-01, Vol.172 (1), p.381-391
• Main Authors: Carlson, Kimberly A, Leisman, Gary, Limoges, Jenae, Pohlman, Garrett D, Horiba, Masahide, Buescher, James, Gendelman, Howard E, Ikezu, Tsuneya
• Format: Article
• Language: English
• Subjects: Adenoviruses, Human - genetics; Amino Acid Sequence; Anti-HIV Agents - chemistry; Anti-HIV Agents - metabolism; Anti-HIV Agents - pharmacology; Cell Line; Cells, Cultured; Cytosol - chemistry; Cytosol - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Down-Regulation - immunology; Gene Expression Regulation, Viral - physiology; HIV-1 - immunology; Human immunodeficiency virus; Humans; Macrophages - metabolism; Macrophages - virology; Molecular Sequence Data; Monocytes - metabolism; Monocytes - virology; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; OTK18 protein; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - immunology; Repressor Proteins - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Terminal Repeat Sequences - immunology; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; transcription suppressors; Virus Replication - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.1.381

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.