Drastic decrease of transcription activity due to hypermutated long terminal repeat (LTR) region in different HIV-1 subtypes and recombinants

Antiviral Res. 2010 Nov;88(2):152-9. doi: 10.1016/j.antiviral.2010.08.007. Epub 2010 Aug 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Expression Regulation, Viral*
  • Genes, Reporter
  • Genes, tat
  • HIV Infections / virology*
  • HIV Long Terminal Repeat / genetics*
  • HIV Protease / genetics
  • HIV-1 / classification
  • HIV-1 / genetics*
  • Humans
  • Luciferases / metabolism
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Sp1 Transcription Factor / metabolism
  • Spain
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic*
  • Transcriptional Activation
  • tat Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • NF-kappa B
  • Sp1 Transcription Factor
  • tat Gene Products, Human Immunodeficiency Virus
  • Luciferases
  • HIV Protease
  • Tetradecanoylphorbol Acetate

Associated data

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