Human immunodeficiency virus type 1 infection inhibits granulocyte-macrophage colony-stimulating factor-induced activation of STAT5A in human monocyte-derived macrophages

J Virol. 2003 Dec;77(23):12630-8. doi: 10.1128/jvi.77.23.12630-12638.2003.

Abstract

Human immunodeficiency virus type 1 (HIV-1) infects cells of the monocyte/macrophage lineage. While infection of macrophages by HIV-1 is generally not cytopathic, it does impair macrophage function. In this study, we examined the effect of HIV-1 infection on intracellular signaling in human monocyte-derived macrophages (MDM) stimulated with the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is an important growth factor for cells of both the macrophage and granulocyte lineages and enhances effector functions of these cells via the heterodimeric GM-CSF receptor (GM-CSFR). A major pathway which mediates the effects of GM-CSF on macrophages involves activation of the latent transcription factor STAT5A via a Janus kinase 2 (JAK2)-dependent pathway. We demonstrate that GM-CSF-induced activation of STAT5A is inhibited in MDM after infection in vitro with the laboratory-adapted R5 strain of HIV-1, HIV-1(Ba-L), but not after infection with adenovirus. HIV-1 infection of MDM did not decrease the STAT5A or JAK2 mRNA level or STAT5A protein level or result in increased constitutive activation of STAT5A. Surface expression of either the alpha-chain or common beta(c)-chain of GM-CSFR was also unaffected. We conclude that HIV-1 inhibits GM-CSF activation of STAT5A without affecting expression of the known components of the signaling pathway. These data provide further evidence of disruption of cellular signaling pathways after HIV-1 infection, which may contribute to immune dysfunction and HIV-1 pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Primers
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • HIV Infections / immunology
  • HIV-1 / physiology*
  • Humans
  • Macrophages / metabolism*
  • Macrophages / virology
  • Milk Proteins*
  • Monocytes / metabolism*
  • Monocytes / virology
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • STAT5 Transcription Factor
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Suppressor Proteins

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • Milk Proteins
  • RNA, Messenger
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Trans-Activators
  • Tumor Suppressor Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor