title: Drastic decrease of transcription activity due to hypermutated long terminal repeat (LTR) region in different HIV-1 subtypes and recombinants.
abstract: Transcriptional activation of HIV-1 gene expression is partially controlled by the interaction between viral and cellular transcription factors acting at HIV-1 long terminal repeat (LTR) sequences. HIV-1 subtyping at LTR region and nucleotide LTR variability from clinical samples in 48 subjects carrying different HIV-1 subtypes (9A, 5C, 3D, 3F, 21G, 2H, 3J and 2 undefined) at the protease (PR) gene, were performed. LTR sequences from each HIV-1 clade were cloned in luciferase-expression vectors to determine basal and Tat-induced transcriptional activities in the presence and absence of PMA stimulation. A high number (37.8%) of recombinants at LTR/PR regions were identified. All HIV-1 promoters presented low basal transcriptional activity that was nevertheless induced by Tat and PMA. LTR activity was similar across the majority of HIV-1 variants in response to Tat and cell activation. Only subtype C and CRF01_AE LTRs presented higher basal and induced-PMA transcription activities than HXB2 clade B promoter. No basal or Tat/PMA induced activity was found in those promoters presenting G to A hypermutation compared to the wild type promoter activities. G to A hypermutation at some important transcription binding-factor sites within LTR compromised the activity of the viral promoter, decreasing the in vitro viral transcription of the luciferase gene.
authors: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain; National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors: Eva Ramírez
authors: ER
authors: de Arellano
authors: José
authors: J
authors: Alcamí
authors: Marisa
authors: M
authors: López
authors: Vincent
authors: V
authors: Soriano
authors: Africa
authors: A
authors: Holguín
mesh_terms: D000328:Adult; D005260:Female; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D015756:Genes, tat; D015658:HIV Infections / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013030:Spain; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D054322:tat Gene Products, Human Immunodeficiency Virus; D008156:Luciferases; D016333:HIV Protease; D013755:Tetradecanoylphorbol Acetate