Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
TRANS-ACTIVATIONS OF GENE EXPRESSION DIRECTED BY THE LONG TERMINAL REPEAT OF THE HUMAN IMMUNODEFICIENCY VIRUS
Vaccines 87. Modern Approaches to New Vaccines: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Chanock RM et al, eds. New York, Cold Spring Harbor Laboratory, p. 125-9, 1987.. Unique Identifier : AIDSLINE ICDB/88647965 Srinivasan A; Rando RF; Pellet P; Peterlin BM; Walker MJ; Barr PJ; Luciw PA; Centers for Disease Control, Atlanta, GA 30333
Abstract:
The recently identified causative agent of acquired immune deficiency syndrome (AIDS) and its prodrome, AIDS-related complex, is a lymphocytopathic retrovirus designated the human immunodeficiency virus (HIV). Regulation of HIV gene expression is complex. The long terminal repeat (LTR) contains several features that are shared by many promoters recognized by eukaryotic RNA polymerase II including a TATA box, upstream elements that bind the transcription factor Sp 1, and an enhancer. HIV gene expression directed by the HIV LTR has been shown to be trans-activated by the virus-coded trans-activator (TAT) gene. The region essential for TAT-mediated trans-activation, the TAT-responsive element (TAR), lies between 17 and +80 in the LTR. Another HIV gene, identified as the antirepression trans-activator (ART) or trans-activator of RNA splicing (TRS), also affects post-transcriptional events in the genesis of viral messages. The LTR-directed gene expression was investigated in tissue culture systems with the aim of identifying cis-acting elements and trans-acting factors involved in the regulation of HIV gene expression. A plasmid containing the HIV-SF2 LTR positioned upstream of the bacterial chloramphenicol transacetylase gene (cat) has been constructed. Transient expression assays are used to measure cat activity in tissue culture cells transfected with various plasmids. In a similar assay system, the interactions of gene products of several DNA viruses with the HIV LTR were examined. It was found that elevated levels of mRNA can account for TAT-mediated trans-activation of the HIV LTR. To analyze the interactions of DNA viruses with HIV, transient expression assays were employed. The assays revealed that DNA viruses contain genes that trans-activate expression directed by the HIV LTR. It appears that more than one region of herpes simplex virus 1 (encoding immediate early genes) can activate the HIV LTR. Plasmids expressing the pseudorabies virus immediate early gene or the adenovirus E1A gene also trans-activate the HIV LTR. Significance of trans-activations of gene activity directed by the HIV LTR is discussed. It has to be determined whether TAT protein acts directly on TAR or whether it functions by affecting synthesis and/or activity of cellular components involved in regulating LTR-directed gene expression. (21 Refs)
Keywords: Cloning, Molecular *Gene Expression Regulation *Genes, Viral Human HIV/*GENETICS Protein Processing, Post-Translational *Repetitive Sequences, Nucleic Acid RNA, Messenger/GENETICS *Terminator Regions (Genetics) Transcription Factors/GENETICS Virus Replication MEETING PAPER
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
