Silencing of Human Immunodeficiency Virus Long Terminal Repeat Expression by an Adenovirus E1a Mutant

Gene expression from the human immunodeficiency virus (HIV) long terminal repeat (LTR) is strongly stimulated by the viral tat gene. The HIV LTR is also activated by several physical and chemical agents and heterologous viral genes, including adenovirus E1a. As E1a has separable transcriptional acti...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1990-02, Vol.87 (4), p.1310-1314
Main Authors: Ventura, Armando M., Arens, Max Q., Srinivasan, A., Chinnadurai, G.
Format: Article
Language:English
Subjects:
Adenovirus Early Proteins
Adenoviruses
Adenoviruses, Human - genetics
AIDS/HIV
Animals
Antigens, Viral, Tumor - genetics
Base Sequence
Cell Line
Chloramphenicol O-Acetyltransferase - genetics
Cloning, Molecular
DNA
Enhancer Elements, Genetic
Gene Expression
Genes, Viral
HeLa Cells
HIV
HIV 1
HIV-1 - genetics
Human T lymphotropic virus 1
Humans
Molecular Sequence Data
Mutation
Oncogene Proteins, Viral - genetics
Plasmids
Repetitive Sequences, Nucleic Acid
Repression
Suppression, Genetic
tat genes
Transactivation
Transcriptional Activation
Transfection
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Summary:Gene expression from the human immunodeficiency virus (HIV) long terminal repeat (LTR) is strongly stimulated by the viral tat gene. The HIV LTR is also activated by several physical and chemical agents and heterologous viral genes, including adenovirus E1a. As E1a has separable transcriptional activation and repression functions, we examined the negative regulatory effects of E1a on the expression of the HIV LTR by using a trans-dominant E1a mutant. Mutant hr5 strongly suppressed the basal activity of the LTR as well as trans-activation of the LTR by heterologous agents such as the cytomegalovirus immediate early gene or DNA-damaging agents such as mitomycin C and UV irradiation. In addition, hr5 also caused significant suppression of that gene-mediated trans-activation. The suppression of HIV LTR expression by hr5 appears to be mediated, at least in part, by the repression of the HIV enhancer, as the activity of an enhancer test system composed of the human T-cell leukemia virus ILTR containing an HIV-1 enhancer substitution was severely repressed by hr5. Cotransfection of HIV-1 proviral DNA with hr5 DNA resulted in a significant reduction of HIV production.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.87.4.1310