OTK18, a zinc -finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions

Masahide Horiba, Lindsey B. Martinez, James L. Buescher, Shinji Sato, Jenae Limoges, Yunquan Jiang, Clinton Jones, Tsuneya Ikezu

Research output: Contribution to journalArticle

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Abstract

It has previously been shown by our laboratory that OTK18, a human immunodeficiency virus (HIV)-inducible zinc-finger protein, reduces progeny-virion production in infected human macrophages. OTK18 antiviral activity is mediated through suppression of Tat-induced HIV-1 long terminal repeat (LTR) promoter activity. Through the use of LTR-scanning mutant vectors, the specific regions responsible for OTK18-mediated LTR suppression have been defined. Two different LTR regions were identified as potential OTK18-binding sites by an enhanced DNA-transcription factor ELISA system; the negative-regulatory element (NRE) at -255/-238 and the Ets-binding site (EBS) at -150/-139 in the LTR. In addition, deletion of the EBS in the LTR blocked OTK18-mediated LTR suppression. These data indicate that OTK18 suppresses LTR activity through two distinct regulatory elements. Spontaneous mutations in these regions might enable HIV-1 to escape from OTK18 antiretroviral activity in human macrophages.

Original languageEnglish (US)
Pages (from-to)236-241
Number of pages6
JournalJournal of General Virology
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2007

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HIV Long Terminal Repeat
Terminal Repeat Sequences
Nucleic Acid Regulatory Sequences
Zinc Fingers
HIV-1
Proteins
Binding Sites
Macrophages
Human Activities
Virion
Antiviral Agents
Transcription Factors
Enzyme-Linked Immunosorbent Assay
HIV
Mutation
DNA

ASJC Scopus subject areas

  • Virology

Cite this

OTK18, a zinc -finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions. / Horiba, Masahide; Martinez, Lindsey B.; Buescher, James L.; Sato, Shinji; Limoges, Jenae; Jiang, Yunquan; Jones, Clinton; Ikezu, Tsuneya.

In: Journal of General Virology, Vol. 88, No. 1, 01.01.2007, p. 236-241.

Research output: Contribution to journalArticle

Horiba, Masahide ; Martinez, Lindsey B. ; Buescher, James L. ; Sato, Shinji ; Limoges, Jenae ; Jiang, Yunquan ; Jones, Clinton ; Ikezu, Tsuneya. / OTK18, a zinc -finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions. In: Journal of General Virology. 2007 ; Vol. 88, No. 1. pp. 236-241.
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