Localization of the Epstein-Barr virus protein LMP 1 to exosomes.
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.
Flanagan
James
J
The Queensland Institute of Medical Research, PO Box Royal Brisbane Hospital, Herston, Queensland 4006, Australia.
Middeldorp
Jaap
J
Department of Pathology, VU Medical Center, Free University, Amsterdam, The Netherlands.
Sculley
Tom
T
Department of Pathology, University of Queensland, St Lucia, Brisbane, Queensland 6067, Australia.|The Queensland Institute of Medical Research, PO Box Royal Brisbane Hospital, Herston, Queensland 4006, Australia.
D001402:B-Lymphocytes; D002461:Cell Line, Transformed; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D016253:Microscopy, Immunoelectron; D015388:Organelles / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins