Modulation of HLA-G expression in human neural cells after neurotropic viral infections

J Virol. 2005 Dec;79(24):15226-37. doi: 10.1128/JVI.79.24.15226-15237.2005.

Abstract

HLA-G is a nonclassical human major histocompatibility complex class I molecule. It may promote tolerance, leading to acceptance of the semiallogeneic fetus and tumor immune escape. We show here that two viruses-herpes simplex virus type 1 (HSV-1), a neuronotropic virus inducing acute infection and neuron latency; and rabies virus (RABV), a neuronotropic virus triggering acute neuron infection-upregulate the neuronal expression of several HLA-G isoforms, including HLA-G1 and HLA-G5, the two main biologically active isoforms. RABV induces mostly HLA-G1, and HSV-1 induces mostly HLA-G3 and HLA-G5. HLA-G expression is upregulated in infected cells and neighboring uninfected cells. Soluble mediators, such as beta interferon (IFN-beta) and IFN-gamma, upregulate HLA-G expression in uninfected cells. The membrane-bound HLA-G1 isoform was detected on the surface of cultured RABV-infected neurons but not on the surface of HSV-1-infected cells. Thus, neuronotropic viruses that escape the host immune response totally (RABV) or partially (HSV-1) regulate HLA-G expression on human neuronal cells differentially. HLA-G may therefore be involved in the escape of certain viruses from the immune response in the nervous system.

MeSH terms

  • HLA Antigens / genetics
  • HLA Antigens / metabolism*
  • HLA-G Antigens
  • Herpesvirus 1, Human / physiology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Nervous System / pathology
  • Nervous System / virology*
  • Neurons / metabolism*
  • Neurons / virology
  • RNA, Messenger / biosynthesis
  • Rabies virus / physiology
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Up-Regulation / immunology

Substances

  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • RNA, Messenger