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Transcriptional activation from the long-terminal repeat of human immunodeficiency virus in vitro
T Okamoto1, T Benter, S F Josephs
1Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Insights
This study investigated human immunodeficiency virus (HIV) transcription regulation. Key elements like the TAR element and GC boxes, along with the tat protein and cellular factors, are crucial for controlling viral gene expression.
Area of Science:
- Molecular Biology
- Virology
- Gene Regulation
Background:
- The human immunodeficiency virus (HIV) long terminal repeat (LTR) controls viral gene transcription.
- Understanding HIV LTR regulation is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the mechanism of trans-acting regulation of transcription from the HIV LTR.
- To evaluate the roles of cis-acting elements and trans-acting factors in HIV transcription.
Main Methods:
- Utilized an in vitro transcription system to analyze HIV LTR activity.
- Assessed the impact of specific DNA sequences (TAR element, GC boxes) and proteins (tat) on transcription.
Main Results:
- Identified the TAR element (+1 to +56) and GC boxes (-77 to -45) within the HIV LTR as essential for transcriptional stimulation.
- Indicated the involvement of the virus-encoded tat protein and cellular factors in regulating HIV transcription.
Conclusions:
- HIV transcription is regulated by a combination of multiple factors, including cis-acting elements and trans-acting proteins.
- This combinatorial regulation provides flexibility for controlled viral gene expression in the provirus.
Abstract:
The mechanism of trans-acting regulation of transcription from the long terminal repeat (LTR) of human immunodeficiency virus (HIV) has been investigated. The roles of the cis-acting elements within HIV LTR, as well as the trans-acting factors present in HIV-infected cells, have been evaluated by an in vitro transcription system. Our observations indicate that both the sequence downstream from the CAP site of HIV LTR (located at nucleotide positions +1 to +56; called the TAR element) and the GC boxes (-77 to -45) are required for full transcriptional stimulation and that both the virus-encoded tat protein and one or more cellular factors might be involved. These results demonstrate the presence of a combinatorial regulation of HIV transcription by multiple factors, which may confer the provirus with greater flexibility in regulated viral gene expression.