A human tumor virus extends its reach

Evaluation of: Meckes DG Jr, Shair KH, Marquitz AR, Kung CP, Edwards RH, Raab-Traub N: Human tumor virus utilizes exosomes for intercellular communication. Proc. Natl Acad. Sci. USA 107(47), 20370–20375 (2010). The article of Meckes et al. evaluated here adds to accumulating evidence that viruses manipulate their environment via the intercellular transfer of viral gene product to recipient cells. The main novelty described in this article is perhaps not that Epstein–Barr virus (EBV)-encoded oncogene latent membrane protein 1 (LMP1) is secreted from tumor cells via small vesicles, but that upon transfer to recipient cells, it activates growth-associated signaling pathways. These vesicles are reminiscent of endocytically-derived exosomes and carry additional cargo besides LMP1, and other important signaling molecules as well. In fact, LMP1 may stimulate the exosomal sorting and secretion of PI3K and EGF receptor proteins by the tumor cells. These signaling molecules are often overexpressed or mutated in epi...

[1]  G. Fogel,et al.  HIV-1 nef protein visits B-cells via macrophage nanotubes: a mechanism for AIDS-related lymphoma pathogenesis? , 2010, Current HIV research.

[2]  N. Raab-Traub,et al.  Human tumor virus utilizes exosomes for intercellular communication , 2010, Proceedings of the National Academy of Sciences.

[3]  T. D. de Gruijl,et al.  Functional delivery of viral miRNAs via exosomes , 2010, Proceedings of the National Academy of Sciences.

[4]  D. Thorley-Lawson,et al.  The Dynamics of EBV Shedding Implicate a Central Role for Epithelial Cells in Amplifying Viral Output , 2009, PLoS pathogens.

[5]  Johan Skog,et al.  Glioblastoma microvesicles transport RNA and protein that promote tumor growth and provide diagnostic biomarkers , 2008, Nature Cell Biology.

[6]  A. Guha,et al.  Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells , 2008, Nature Cell Biology.

[7]  S. Ceccarelli,et al.  Epstein‐Barr virus latent membrane protein 1 promotes concentration in multivesicular bodies of fibroblast growth factor 2 and its release through exosomes , 2007, International journal of cancer.

[8]  Y. Shimizu,et al.  A New Diagnostic Marker for Secreted Epstein-Barr Virus–Encoded LMP1 and BARF1 Oncoproteins in the Serum and Saliva of Patients with Nasopharyngeal Carcinoma , 2007, Clinical Cancer Research.

[9]  D. Pegtel,et al.  Epstein-Barr Virus Infection in Ex Vivo Tonsil Epithelial Cell Cultures of Asymptomatic Carriers , 2004, Journal of Virology.

[10]  D. Thorley-Lawson,et al.  Persistence of the Epstein-Barr virus and the origins of associated lymphomas. , 2004, The New England journal of medicine.

[11]  Jaap M Middeldorp,et al.  Localization of the Epstein-Barr virus protein LMP 1 to exosomes. , 2003, The Journal of general virology.

[12]  B. Sugden,et al.  LMP1, a viral relative of the TNF receptor family, signals principally from intracellular compartments , 2003, The EMBO journal.

[13]  W. Hammerschmidt,et al.  Latent membrane protein 1 is critical for efficient growth transformation of human B cells by epstein-barr virus. , 2003, Cancer research.

[14]  A. Ciechanover,et al.  Degradation of the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) by the Ubiquitin-Proteasome Pathway , 2000, The Journal of Biological Chemistry.

[15]  E. Bloemena,et al.  Direct Immunosuppressive Effects of EBV-Encoded Latent Membrane Protein 1 , 2000, The Journal of Immunology.

[16]  D. Thorley-Lawson,et al.  Posttranslational processing of the Epstein-Barr virus-encoded p63/LMP protein , 1987, Journal of virology.