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

James Flanagan, Jaap Middeldorp, Tom Sculley

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1871-9
Number of pages9
JournalJournal of General Virology
Volume84
Issue numberPt 7
DOIs
Publication statusPublished - Jul 2003

Cite this

Flanagan, James ; Middeldorp, Jaap ; Sculley, Tom. / Localization of the Epstein-Barr virus protein LMP 1 to exosomes. In: Journal of General Virology. 2003 ; Vol. 84, No. Pt 7. pp. 1871-9.
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Localization of the Epstein-Barr virus protein LMP 1 to exosomes. / Flanagan, James; Middeldorp, Jaap; Sculley, Tom.

In: Journal of General Virology, Vol. 84, No. Pt 7, 07.2003, p. 1871-9.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Middeldorp, Jaap

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AB - 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.

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KW - Golgi Apparatus

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KW - Humans

KW - Microscopy, Immunoelectron

KW - Organelles

KW - Tumor Cells, Cultured

KW - Viral Matrix Proteins

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