{"doi":"10.1128/jvi.01384-08","title":"O-Linked\n                    <i>N</i>\n                    -Acetylglucosaminylation of Sp1 Inhibits the Human Immunodeficiency Virus Type 1 Promoter","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>\n                    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                    <jats:italic>N</jats:italic>\n                    -acetyl-\n                    <jats:sc>d</jats:sc>\n                    -glucosamine (\n                    <jats:italic>O</jats:italic>\n                    -GlcNAc), we evaluated whether increased\n                    <jats:italic>O</jats:italic>\n                    -GlcNAcylation affects HIV-1 transcription. In the present study we demonstrate that treatment of HIV-1-infected lymphocytes with the\n                    <jats:italic>O</jats:italic>\n                    -GlcNAcylation-enhancing agent glucosamine (GlcN) repressed viral transcription in a dose-dependent manner. Overexpression of\n                    <jats:italic>O</jats:italic>\n                    -GlcNAc transferase (OGT), the sole known enzyme catalyzing the addition of\n                    <jats:italic>O</jats:italic>\n                    -GlcNAc to proteins, specifically inhibited the activity of the HIV-1 LTR promoter in different T-cell lines and in primary CD4\n                    <jats:sup>+</jats:sup>\n                    T lymphocytes. Inhibition of HIV-1 LTR activity in infected T cells was most efficient (&gt;95%) when OGT was recombinantly overexpressed prior to infection.\n                    <jats:italic>O</jats:italic>\n                    -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\n                    <jats:italic>O</jats:italic>\n                    -GlcNAcylation of Sp1 inhibits the activity of the HIV-1 LTR promoter. Modulation of Sp1\n                    <jats:italic>O</jats:italic>\n                    -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.\n                  </jats:p>","journal":"Journal of Virology","year":2009,"id":15196,"datarank":2.13607549177379,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":1.5754250490312847,"self_endowment_contribution":0.5606504427425053,"citer_contribution":1.5754250490312847,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":40,"citers_with_citation_signal":37,"citers_with_endowment":37,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":116895,"name":"Mathias Thurau","orcid":null,"position":1,"is_corresponding":false},{"id":116897,"name":"Susan Jung","orcid":null,"position":2,"is_corresponding":false},{"id":116898,"name":"Christian Hofmann","orcid":null,"position":3,"is_corresponding":false},{"id":116899,"name":"Elisabeth Naschberger","orcid":null,"position":4,"is_corresponding":false},{"id":116900,"name":"Elisabeth Kremmer","orcid":null,"position":5,"is_corresponding":false},{"id":116901,"name":"Thomas Harrer","orcid":null,"position":6,"is_corresponding":false},{"id":105674,"name":"Matthew Miller","orcid":"0000-0002-3267-6510","position":7,"is_corresponding":false},{"id":116902,"name":"Niels Schaft","orcid":null,"position":8,"is_corresponding":false},{"id":116903,"name":"Michael Stürzl","orcid":null,"position":9,"is_corresponding":false},{"id":116893,"name":"Ramona Jochmann","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19193796","pmcid":"PMC2663287","openalex_id":"https://openalex.org/W2141735396","authors":[],"funders":[],"total_grants":0,"fwci":1.5436,"citation_percentile":0.82751745,"influential_citations":3,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":3},{"year":2014,"count":3},{"year":2015,"count":2},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":6},{"year":2022,"count":1},{"year":2024,"count":3},{"year":2025,"count":2}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2663287","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc2663287?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2663287","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.01384-08","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.01384-08","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19193796","host_type":"repository"},{"url":"https://open.fau.de/handle/openfau/867","host_type":""},{"url":"https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=2016","host_type":"repository"},{"url":"https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/867","host_type":"repository"}],"fields_of_study":["HIV Research and Treatment","Glycosylation and Glycoproteins Research","Carbohydrate Chemistry and Synthesis","Medicine","Biology","Acetylglucosamine","CD4-Positive T-Lymphocytes","Cell Line","Cells, Cultured","Gene Dosage","Gene Expression Regulation, Viral","Glycosylation","HIV Long Terminal Repeat","HIV-1","Humans","N-Acetylglucosaminyltransferases","Sp1 Transcription Factor","Virus Replication"],"mesh_terms":["Acetylglucosamine","Cell Line","Cells, Cultured","Glycosylation","Humans","Virus Replication","CD4-Positive T-Lymphocytes","HIV-1","Gene Expression Regulation, Viral","HIV Long Terminal Repeat","Sp1 Transcription Factor","N-Acetylglucosaminyltransferases","Gene Dosage"],"keywords":["Biology","Virology","Human immunodeficiency virus (HIV)","Promoter","Genetics","Gene","Gene expression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"refseq"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T16:46:36.042993Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}