{"doi":"10.1128/jvi.68.2.1229-1233.1994","title":"Adeno-associated virus type 2 rep gene-mediated inhibition of basal gene expression of human immunodeficiency virus type 1 involves its negative regulatory functions","abstract":"<jats:p>Adeno-associated virus type 2 (AAV-2), a human parvovirus which is apathogenic in adults, inhibits replication and gene expression of human immunodeficiency virus type 1 (HIV-1) in human cells. The rep gene of AAV-2, which was shown earlier to be sufficient for this negative interference, also down-regulated the expression of heterologous sequences driven by the long terminal repeat (LTR) of HIV-1. This effect was observed in the absence of the HIV-1 transactivator Tat, i.e., at basal levels of LTR-driven transcription. In this work, we studied the involvement of functional subsequences of the HIV-1 LTR in rep-mediated inhibition in the absence of Tat. Mutated LTRs driving an indicator gene (cat) were cointroduced into human SW480 cells together with rep alone or with double-stranded DNA fragments or RNA containing sequences of the HIV-1 LTR. The results indicate that rep strongly enhances the function of negative regulatory elements of the LTR. In addition, the experiments revealed a transcribed sequence element located within the TAR-coding sequence termed AHHH (AAV-HIV homology element derived from HIV-1) which is involved in rep-mediated inhibition. The AHHH element is also involved in down-regulation of basal expression levels in the absence of rep, suggesting that AHHH also contributes to negative regulatory functions of the LTR of HIV-1. In contrast, positive regulatory elements of the HIV-1 LTR such as the NF kappa B and SP1 binding sites have no significant influence on the rep-mediated inhibition.</jats:p>","journal":"Journal of Virology","year":1994,"id":14715,"datarank":1.940251404270583,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":1.4300717970212595,"self_endowment_contribution":0.5101796072493234,"citer_contribution":1.4300717970212595,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":28,"citers_with_citation_signal":28,"citers_with_endowment":28,"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":115066,"name":"K Rittner","orcid":null,"position":1,"is_corresponding":false},{"id":115067,"name":"G Sczakiel","orcid":null,"position":2,"is_corresponding":false},{"id":115065,"name":"I Oelze","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"8289357","pmcid":"PMC236567","openalex_id":"https://openalex.org/W1645190013","authors":[],"funders":[],"total_grants":0,"fwci":3.9035,"citation_percentile":0.93570227,"influential_citations":5,"citation_trend":[{"year":2017,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://jvi.asm.org/content/jvi/68/2/1229.full.pdf","host_type":"journal"},{"url":"https://doi.org/10.1128/jvi.68.2.1229-1233.1994","host_type":"BRONZE"},{"url":"https://jvi.asm.org/content/jvi/68/2/1229.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/jvi.68.2.1229-1233.1994","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8289357","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC236567","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/236567","host_type":"repository"}],"fields_of_study":["Virus-based gene therapy research","HIV Research and Treatment","RNA Research and Splicing","Biology","Medicine","Base Sequence","Cells, Cultured","DNA Mutational Analysis","DNA-Binding Proteins","Dependovirus","Gene Expression Regulation, Viral","Gene Products, tat","Genes, Reporter","Genes, Viral","HIV Long Terminal Repeat","HIV-1","Humans","Molecular Sequence Data","Transcription, Genetic","Viral Proteins","tat Gene Products, Human Immunodeficiency Virus"],"mesh_terms":["Dependovirus","Base Sequence","Cells, Cultured","DNA Mutational Analysis","DNA-Binding Proteins","Genes, Viral","Humans","Molecular Sequence Data","Transcription, Genetic","Viral Proteins","HIV-1","Gene Products, tat","Gene Expression Regulation, Viral","HIV Long Terminal Repeat","Genes, Reporter","tat Gene Products, Human Immunodeficiency Virus"],"keywords":["Biology","Long terminal repeat","Transactivation","Regulatory sequence","Gene","HIV Long Terminal Repeat","Negative regulatory element","Gene expression","Transcription (linguistics)","Regulation of gene expression","Molecular biology","Enhancer","Virus","Genetics","Virology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T13:58:38.865716Z","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":[]}