O-linked N-acetylglucosaminylation of Sp1 inhibits the human immunodeficiency virus type 1 promoter
Jochmann R, Thurau M, Jung S, Hofmann C, Naschberger E, Kremmer E, Harrer T, Miller M, Schaft N, Stürzl M (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 83
Pages Range: 3704-3718
Journal Issue: 8
DOI: 10.1128/JVI.01384-08
Abstract
Human immunodeficiency virus type 1 (HIV-1) gene expression and replication are regulated by the promoter/enhancer located in the U3 region of the proviral 5′ long terminal repeat (LTR). The binding of cellular transcription factors to specific regulatory sites in the 5′ LTR is a key event in the replication cycle of HIV-1. Since transcriptional activity is regulated by the posttranslational modification of transcription factors with the monosaccharide O-linked N-acetyl-D-glucosamine (O-GlcNAc), we evaluated whether increased O-GlcNAcylation affects HIV-1 transcription. In the present study we demonstrate that treatment of HIV-1-infected lymphocytes with the O-GlcNAcylation-enhancing agent glucosamine (GlcN) repressed viral transcription in a dose-dependent manner. Overexpression of O-GlcNAc transferase (OGT), the sole known enzyme catalyzing the addition of O-GlcNAc to proteins, specifically inhibited the activity of the HIV-1 LTR promoter in different T-cell lines and in primary CD4+ T lymphocytes. Inhibition of HIV-1 LTR activity in infected T cells was most efficient (>95%) when OGT was recombinantly overexpressed prior to infection. O-GlcNAcylation of the transcription factor Sp1 and the presence of Sp1-binding sites in the LTR were found to be crucial for this inhibitory effect. From this study, we conclude that O-GlcNAcylation of Sp1 inhibits the activity of the HIV-1 LTR promoter. Modulation of Sp1 O-GlcNAcylation may play a role in the regulation of HIV-1 latency and activation and links viral replication to the glucose metabolism of the host cell. Hence, the establishment of a metabolic treatment might supplement the repertoire of antiretroviral therapies against AIDS. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Authors with CRIS profile
Susan Jung
Department of Paediatrics and Adolescent Medicine
Christian Hofmann
Lehrstuhl für Medizinische Physik und Mikrogewebetechnik
Elisabeth Naschberger
Medizinische Fakultät
Thomas Harrer
Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz
Niels Schaft
Department of Dermatology
Michael Stürzl
Professur für Molekulare und Experimentelle Chirurgie
Involved external institutions
Germany (DE)How to cite
APA:
Jochmann, R., Thurau, M., Jung, S., Hofmann, C., Naschberger, E., Kremmer, E.,... Stürzl, M. (2009). O-linked N-acetylglucosaminylation of Sp1 inhibits the human immunodeficiency virus type 1 promoter. Journal of Virology, 83(8), 3704-3718. https://doi.org/10.1128/JVI.01384-08
MLA:
Jochmann, Ramona, et al. "O-linked N-acetylglucosaminylation of Sp1 inhibits the human immunodeficiency virus type 1 promoter." Journal of Virology 83.8 (2009): 3704-3718.
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