Improved gene expression in resting macrophages using an oligopeptide derived from Vpr of human immunodeficiency virus type-1

Biochem Biophys Res Commun. 2005 Dec 23;338(3):1499-506. doi: 10.1016/j.bbrc.2005.10.112. Epub 2005 Oct 27.

Abstract

Vpr, an accessory gene product of human immunodeficiency virus type-1, is thought to transport a viral DNA from the cytoplasm to the nucleus in resting macrophages. Previously, we reported that a peptide encompassing amino acids 52-78 of Vpr (C45D18) promotes the nuclear trafficking of recombinant proteins that are conjugated with C45D18. Here, we present evidence that C45D18, when conjugated with a six-branched cationic polymer of poly(N,N-dimethylaminopropylacrylamide)-block-oligo(4-aminostyrene) (SV: star vector), facilitates gene expression in resting macrophages. Although there was no difference between SV alone and C45D18-SV with respect to gene transduction into growing cells, C45D18-SV resulted in more than 40-fold greater expression of the exogenous gene upon transduction into chemically differentiated macrophages and human quiescent monocyte-derived macrophages. The data suggest that C45D18 contributes to improving the ability of a non-viral vector to transduce macrophages with exogenous genes and we discuss its further application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line, Tumor
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • DNA / genetics
  • Gene Expression / drug effects*
  • Gene Expression / genetics
  • Gene Products, vpr / chemistry*
  • HIV-1 / chemistry*
  • HIV-1 / genetics
  • Humans
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology*
  • vpr Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, vpr
  • Peptide Fragments
  • vpr Gene Products, Human Immunodeficiency Virus
  • DNA