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Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication
Vanessa Brès1, Rosemary Kiernan, Stéphane Emiliani
1Institut de Génétique Humaine, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier cedex 5, France.
The Journal of Biological Chemistry
|April 17, 2002
Summary
Acetylation of human immunodeficiency virus type-1 Tat protein at lysines 28 and 50 is crucial for viral replication and trans-activation. Mutating these sites impacts HIV-1 promoter activity and virus spread.
Area of Science:
- Molecular Biology
- Virology
- Epigenetics
Background:
- Human immunodeficiency virus type-1 (HIV-1) trans-activator Tat is essential for viral transcription.
- Tat activates the HIV-1 promoter by binding the trans-activation-responsive region (TAR).
- Histone acetyltransferases (HATs) like p300, p300/CBP-associating factor, and hGCN5 acetylate Tat.
Purpose of the Study:
- To investigate the functional significance of Tat acetylation at specific lysine residues.
- To determine the impact of mutating acetyl-acceptor lysines on HIV-1 replication and Tat-mediated trans-activation.
Main Methods:
- Site-directed mutagenesis of Tat protein at lysine 28 and lysine 50 to arginine or glutamine.
- Assessment of HIV-1 replication in cells expressing mutated Tat.
- Analysis of Tat trans-activation of integrated and nonintegrated long terminal repeat (LTR) promoters.
Main Results:
- Mutation of lysine 28 and lysine 50 to non-acetylatable residues significantly affected HIV-1 replication.
- Mutations differentially impacted Tat trans-activation of integrated versus nonintegrated LTRs.
- Lysine 28 and lysine 50 are critical for Tat function in viral replication.
Conclusions:
- Acetylation of Tat at lysine 28 and lysine 50 plays a vital role in HIV-1 replication.
- These acetylation sites are important for Tat's ability to trans-activate the viral promoter.
- Targeting Tat acetylation could be a potential strategy for HIV-1 therapy.