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

Authors

Masahide Horiba, University of Nebraska Medical Center, Omaha, NE
Lindsey B. Martinez, University of Nebraska Medical Center, Omaha, NE
James L. Buescher, University of Nebraska Medical Center, Omaha, NE
Sinji Sato, University of Nebraska Medical Center, Omaha, NE
Jenae Limoges, University of Nebraska Medical Center, Omaha, NE
Yunquan Jiang, University of Nebraska - Lincoln
Clinton J. Jones, University of Nebraska - LincolnFollow
Tsuneya Ikezu, University of Nebraska Medical Center, Omaha, NE

Document Type

Article

Date of this Version

October 2007

Comments

Published in Journal of General Virology 88 (2007), 236-241; DOI 10.1099/vir.0.82066-0 Copyright © 2007 Society for General Microbiology. Used by permission.

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 identifi ed 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.