TY - JOUR
T1 - OTK18, a zinc -finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions
AU - Horiba, Masahide
AU - Martinez, Lindsey B.
AU - Buescher, James L.
AU - Sato, Shinji
AU - Limoges, Jenae
AU - Jiang, Yunquan
AU - Jones, Clinton
AU - Ikezu, Tsuneya
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
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U2 - 10.1099/vir.0.82066-0
DO - 10.1099/vir.0.82066-0
M3 - Article
C2 - 17170456
AN - SCOPUS:33846165427
SN - 0022-1317
VL - 88
SP - 236
EP - 241
JO - Journal of General Virology
JF - Journal of General Virology
IS - 1
ER -