HIV-1 Vpr binding to HIV-1 LTR C/EBP cis-acting elements and adjacent regions is sequence-specific

Biomed Pharmacother. 2003 Jan;57(1):41-8. doi: 10.1016/s0753-3322(02)00333-5.

Abstract

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a 14 kDa virion-associated protein that transactivates the HIV-1 long terminal repeat (LTR) as well as other eukaryotic promoters. Vpr also functions in nuclear localization and import of the HIV-1 preintegration complex (PIC), cell cycle arrest at the G(2)/M interface, and virion packaging. Electrophoretic mobility shift analysis has been utilized to demonstrate a direct association between purified Vpr (strain pNL4-3) and HIV-1 LTR sequences that span the adjacent C/EBP site I, NF-kappaB site II, and ATF/CREB binding site (nt -95 to -130, relative to the start of transcription). A similar interaction has been observed between HIV-1 Vpr and LTR C/EBP site II (nt -167 to -175). A total of 94.7% of LTRs derived from peripheral blood contained C/EBP site I variants that displayed a high relative Vpr binding affinity phenotype, while only 5.3% exhibited a low relative Vpr binding affinity phenotype. All LTRs derived from peripheral blood exhibited a high relative Vpr binding phenotype at C/EBP site II. These results suggest a preference for the maintenance of two cis-acting elements with high affinity for Vpr within LTRs derived from peripheral blood. Additional studies have also demonstrated that naturally occurring sequence variation within C/EBP site I and II can dramatically alter the relative affinity of Vpr for these cis-acting elements. These studies suggest that Vpr may regulate the interaction of members of the C/EBP transcription factor family with the viral LTR.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Electrophoretic Mobility Shift Assay / methods
  • Gene Products, vpr / genetics
  • Gene Products, vpr / metabolism*
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • Humans
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Protein Binding
  • Sequence Homology, Nucleic Acid
  • U937 Cells
  • vpr Gene Products, Human Immunodeficiency Virus

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Gene Products, vpr
  • Oligonucleotides
  • vpr Gene Products, Human Immunodeficiency Virus