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M9650423.TXT
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1996-03-09
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Document 0423
DOCN M9650423
TI Essential role of NF-kappa B in transactivation of the human
immunodeficiency virus long terminal repeat by the human cytomegalovirus
1E1 protein.
DT 9605
AU Kim S; Yu SS; Kim VN; Institute for Molecular Biology and Genetics,
Seoul National; University, Kwan-Ak-Gu, Korea.
SO J Gen Virol. 1996 Jan;77 ( Pt 1):83-91. Unique Identifier : AIDSLINE
MED/96145137
AB The 72 kDa 1E1 protein of human cytomegalovirus (HCMV) is one of a few
viral regulatory proteins expressed immediately after infection of a
host cell. Although it is now well-established that 1E1 is a potent
transcriptional activator of the human immunodeficiency virus (HIV) long
terminal repeat (LTR), the identity of the nucleotide sequence
responsive to 1E1 remains elusive and the molecular mechanism of this
interaction is not well-understood. We have constructed various LTR
mutants and tested them for their ability to be activated by 1E1 using
transient transfection assays. Mutations in the NF-kappa B sites, of
either a few changes in the nucleotide sequence or a deletion of the
entire region, abrogated 1E1-driven transactivation. Deletion of the
Tat-responsive element (TAR) had no significant effect on reporter
expression. Mutations in the Sp1 sites or the TATA box significantly
lowered LTR activity, but this is probably due to an effect on the
general transcription system, as these elements are also required for
the transactivation of the LTR by many stimulators including Tat, tumour
necrosis factor alpha (TNF-alpha). E1A/E1B and phorbol myristate acetate
(PMA). In addition, gel retardation analysis demonstrated that NF- kappa
B activity was significantly increased in human T lymphoid H9 and
monocytic U937 cell lines constitutively expressing 1E1. Taken together,
these data suggest that NF- kappa B plays a central role in the 1E1
transactivation of the HIV LTR.
DE Base Sequence Cell Line Down-Regulation (Physiology) Gene Expression
Regulation, Viral Genetic Vectors Hela Cells Human HIV/*GENETICS
HIV Long Terminal Repeat/*GENETICS Immediate-Early
Proteins/GENETICS/*METABOLISM Molecular Sequence Data NF-kappa
B/GENETICS/*METABOLISM Regulatory Sequences, Nucleic Acid Sequence
Deletion Support, Non-U.S. Gov't *Trans-Activation (Genetics)
Transcription, Genetic JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).