CSF-induced and HIV-1-mediated distinct regulation of Hck and C/EBPbeta represent a heterogeneous susceptibility of monocyte-derived macrophages to M-tropic HIV-1 infection

J Exp Med. 2003 Aug 4;198(3):443-53. doi: 10.1084/jem.20022018.

Abstract

Granulocyte/macrophage colony-stimulating factor (GM-CSF)-induced monocyte-derived macrophages (GM-MPhi) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MPhi) produce a large amount of HIV-1. M-MPhi express a high level of Hck and a large isoform of C/EBPbeta, and HIV-1 infection increases the expression of Hck but not of C/EBPbeta. GM-MPhi express a high level of C/EBPbeta and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPbeta but decreases that of Hck. Treatment of M-MPhi with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPbeta and inhibits the viral replication. Treatment of GM-MPhi with a moderate amount of AS-C/EBPbeta not only inhibits the expression of the small isoform of C/EBPbeta preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1-mediated distinct regulation of Hck and small isoform of C/EBPbeta represent the heterogeneous susceptibility of tissue MPhi to HIV-1 infection, and the regulation of Hck and C/EBPbeta are closely related and these two molecules affect one another.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • HIV-1 / physiology*
  • Humans
  • Lymphocyte Activation
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / virology*
  • Monocytes / physiology
  • Oligonucleotides, Antisense / metabolism
  • Protein Biosynthesis
  • Protein Isoforms / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-hck
  • Virus Replication

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Oligonucleotides, Antisense
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Protein-Tyrosine Kinases
  • HCK protein, human
  • Proto-Oncogene Proteins c-hck