Localization of the Epstein-Barr virus protein LMP 1 to exosomes

J Gen Virol. 2003 Jul;84(Pt 7):1871-1879. doi: 10.1099/vir.0.18944-0.

Abstract

The Epstein-Barr virus latent membrane protein (LMP 1) functions as a constitutively active signalling molecule and associates in lipid rafts clustered with other signalling molecules. Using immunofluorescent confocal microscopy, LMP 1 was shown to have an heterogeneous distribution among individual cells which was not related to the cell cycle stage. LMP 1 was shown to localize to intracellular compartments in cells other than the plasma membrane. Co-labelling of cells with both an LMP 1 antibody and an antibody to the Golgi protein GS15 revealed that the intracellular LMP 1 partly co-localized with the Golgi apparatus. Further confirmation of intracellular LMP 1 localization was obtained by immunoelectron microscopy with rabbit polyclonal LMP 1 antibodies and cryosectioning. As well as being present in intracellular foci, LMP 1 co-localized in part with MHC-II and was present on exosomes derived from a lymphoblastoid cell line. Preparations of LMP 1 containing exosomes were shown to inhibit the proliferation of peripheral blood mononuclear cells, suggesting that LMP 1 could be involved in immune regulation. This may be of particular relevance in EBV-associated tumours such as nasopharyngeal carcinoma and Hodgkin's disease, as LMP 1-containing exosomes may be taken up by infiltrating T-lymphocytes, where LMP 1 could exert an anti-proliferative effect, allowing the tumour cells to evade the immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes
  • Cell Line, Transformed
  • Fluorescent Antibody Technique
  • Golgi Apparatus / metabolism
  • Herpesvirus 4, Human / metabolism*
  • Herpesvirus 4, Human / physiology
  • Humans
  • Microscopy, Immunoelectron
  • Organelles / metabolism*
  • Tumor Cells, Cultured
  • Viral Matrix Proteins / metabolism*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • Viral Matrix Proteins