Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome

Nucleic Acids Res. 2016 Jul 27;44(13):6442-51. doi: 10.1093/nar/gkw432. Epub 2016 Jun 13.

Abstract

The long terminal repeat (LTR) of the proviral human immunodeficiency virus (HIV)-1 genome is integral to virus transcription and host cell infection. The guanine-rich U3 region within the LTR promoter, previously shown to form G-quadruplex structures, represents an attractive target to inhibit HIV transcription and replication. In this work, we report the structure of a biologically relevant G-quadruplex within the LTR promoter region of HIV-1. The guanine-rich sequence designated LTR-IV forms a well-defined structure in physiological cationic solution. The nuclear magnetic resonance (NMR) structure of this sequence reveals a parallel-stranded G-quadruplex containing a single-nucleotide thymine bulge, which participates in a conserved stacking interaction with a neighboring single-nucleotide adenine loop. Transcription analysis in a HIV-1 replication competent cell indicates that the LTR-IV region may act as a modulator of G-quadruplex formation in the LTR promoter. Consequently, the LTR-IV G-quadruplex structure presented within this work could represent a valuable target for the design of HIV therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • G-Quadruplexes*
  • Genome, Viral
  • Guanine / metabolism
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / chemistry*
  • HIV-1 / genetics
  • HIV-1 / pathogenicity
  • Humans
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation*
  • Promoter Regions, Genetic
  • Proviruses / chemistry
  • Proviruses / genetics
  • Proviruses / pathogenicity

Substances

  • Guanine