Extracellular vesicles from infected cells: Potential for direct pathogenesis

Frontiers in Microbiology

Volumn 6, Issue OCT, 2015, Pages

  Schwab, Angela ^a   Meyering, Shabana S ^a,b   Lepene, Ben ^c   Iordanskiy, Sergey ^a   van Hoek, Monique L ^a   Hakami, Ramin M ^a   Kashanchi, Fatah ^a  

^a GEORGE MASON UNIVERSITY   (United States)

^b GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^c CERES NANOSCIENCES INC   (United States)

Author keywords

Bacteria; Exosome; Extracellular vesicle; Parasite; Pathogen; Protozoa; Virus

Indexed keywords

BIOLOGICAL MARKER; TOLL LIKE RECEPTOR; VACCINE;

APOPTOSIS; BACTERIAL MEMBRANE; BACTERIAL VIRULENCE; CD4+ T LYMPHOCYTE; CENTRIFUGATION; EPSTEIN BARR VIRUS; EXOSOME; GENE EXPRESSION; HEPATITIS C VIRUS; HERPES SIMPLEX VIRUS; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; IMMUNE SYSTEM; INFECTION; MEMBRANE VESICLE; NONHUMAN; PATHOGENESIS; POLYMERASE CHAIN REACTION; PROTEOMICS; PURIFICATION; REVIEW;

EID: 84946893719     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2015.01132     Document Type: Review

References (166)

1. Abrami, L., Brandi, L., Moayeri, M., Brown, M. J., Krantz, B. A., Leppla, S. H., et al. (2013). Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin. Cell Rep. 5, 986-996. doi: 10.1016/j.celrep.2013.10.019
2. Aga, M., Bentz, G. L., Raffa, S., Torrisi, M. R., Kondo, S., Wakisaka, N., et al. (2014). Exosomal HIFa supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes. Oncogene 33, 4613-4622. doi: 10.1038/onc.2014.66
3. Ahmed, W., Philip, P. S., Tariq, S., and Khan, G. (2014). Epstein-Barr virus-encoded small RNAs (EBERs) are present in fractions related to exosomes released by EBV-transformed cells. PLoS ONE 9:e99163. doi: 10.1371/journal.pone.0099163
4. Akers, J. C., Gonda, D., Kim, R., Carter, B. S., and Chen, C. C. (2013). Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like and apoptotic bodies. J. Neurooncol. 113, 1-11. doi: 10.1007/s11060-013-1084-8
5. Aline, F., Bout, D., Amigorena, S., Roingeard, P., and Dimier-Poisson, I. (2004). Toxoplasma gondii antigen-pulsed-dendritic cell-derived exosomes induce a protective immune response against T. gondii infection. Infect. Immun. 72, 4127-4137. doi: 10.1128/IAI.72.7.4127-4137.2004
6. Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., and Wood, M. J. (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341-345. doi: 10.1038/nbt.1807
7. Ansari, M. A., Singh, V. V., Dutta, S., Veettil, M. V., Dutta, D., Chikoti, L., et al. (2013). Constitutive interferon-inducible protein 16-inflammasome activation during Epstein-Barr virus latency I, II, and III in B and epithelial cells. J. Virol. 87, 8606-8623. doi: 10.1128/JVI.00805-13
8. Arenaccio, C., Chiozzini, C., Columba-Cabezas, S., Manfredi, F., Affabris, E., Baur, A., et al. (2014). Exosomes from human immunodeficiency virus type 1 (HIV-1)-infected cells license quiescent CD4+ T lymphocytes to replicate HIV-1 through a Nef-and ADAM17-dependent mechanism. J. Virol. 88, 11529-11539. doi: 10.1128/JVI.01712-14
9. Ariza, M. E., Rivailler, P., Glaser, R., Chen, M., and Williams, M. V. (2013). Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. PLoS ONE 8:e69827. doi: 10.1371/journal.pone.0069827
10. Bai, W., Liu, H., Ji, Q., Zhou, Y., Liang, L., Zheng, R., et al. (2014). TLR3 regulates mycobacterial RNA-induced IL-10 production through the PI3K/AKT signaling pathway. Cell. Signal. 26, 942-950. doi: 10.1016/j.cellsig.2014.01.015
11. Barth, S., Meister, G., and Grasser, F. A. (2011). EBV-encoded miRNAs. Biochim. Biophys. Acta 1809, 631-640. doi: 10.1016/j.bbagrm.2011.05.010
12. Beatty, W. L., Rhoades, E. R., Ullrich, H. J., Chatterjee, D., Heuser, J. E., and Russell, D. G. (2000). Trafficking and release of mycobacterial lipids from infected macrophages. Traffic 1, 235-247. doi: 10.1034/j.1600-0854.2000.010306.x
13. Beatty, W. L., Ullrich, H. J., and Russell, D. G. (2001). Mycobacterial surface moieties are released from infected macrophages by a constitutive exocytic event. Eur. J. Cell Biol. 80, 31-40. doi: 10.1078/0171-9335-00131
14. Beauvillain, C., Juste, M. O., Dion, S., Pierre, J., and Dimier-Poisson, I. (2009). Exosomes are an effective vaccine against congenital toxoplasmosis in mice. Vaccine 27, 1750-1757. doi: 10.1016/j.vaccine.2009.01.022
15. Berleman, J., and Auer, M. (2013). The role of bacterial outer membrane vesicles for intra-and interspecies delivery. Environ. Microbiol. 15, 347-354. doi: 10.1111/1462-2920.12048
16. Bernal, D., Trelis, M., Montaner, S., Cantalapiedra, F., Galiano, A., Hackenberg, M., et al. (2014). Surface analysis of Dicrocoelium dendriticum. The molecular characterization of exosomes reveals the presence of miRNAs. J. Proteomics 105, 232-241. doi: 10.1016/j.jprot.2014.02.012
17. Bhatnagar, S., and Schorey, J. S. (2007). Exosomes released from infected macrophages contain Mycobacterium avium glycopeptidolipids and are proinflammatory. J. Biol. Chem. 282, 25779-25789. doi: 10.1074/jbc.M702277200
18. Bhatnagar, S., Shinagawa, K., Castellino, F. J., and Schorey, J. S. (2007). Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 110, 3234-3244. doi: 10.1182/blood-2007-03-079152
19. Brown, L., Kessler, A., Cabezas-Sanchez, P., Lugue-Garcia, J. L., and Casadevall, A. (2014). Extracellular vesicles produced by the Gram-positive bacterium Bacillus subtilis are disrupted by the lipopeptide surfactin. Mol. Microbiol. 93, 183-198. doi: 10.1111/mmi.12650
20. Bruggmann, P., Falcato, L., Dober, S., Helbling, B., Keiser, O., Negro, F., et al. (2008). Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients. J. Viral. Hepat. 15, 747-752. doi: 10.1111/j.1365-2893.2008.01010.x
21. Buck, A. H., Coakley, G., Simbari, F., Mcsorley, H. J., Quintana, J. F., Le Bihan, T., et al. (2014). Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat Commun. 5, 5488. doi: 10.1038/ncomms6488
22. Bukong, T. N., Momen-Heravi, F., Kodys, K., Bala, S., and Szabo, G. (2014). Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90. PLoS Pathog. 10:e1004424. doi: 10.1371/journal.ppat.1004424
23. Canitano, A., Venturi, G., Borghi, M., Ammendolia, M. G., and Fais, S. (2013). Exosomes released in vitro from Epstein-Barr virus (EBV)-infected cells contain EBV-encoded latent phase mRNAs. Cancer Lett. 337, 193-199. doi: 10.1016/j.canlet.2013.05.012
24. Catanese, M. T., Uryu, K., Kopp, M., Edwards, T. J., Andrus, L., Rice, W. J., et al. (2013). Ultrastructural analysis of hepatitis C virus particles. Proc. Natl. Acad. Sci. U.S.A. 110, 9505-9510. doi: 10.1073/pnas.1307527110
25. Ceccarelli, S., Visco, V., Raffa, S., Wakisaka, N., Pagano, J. S., and Torrisi, M. R. (2007). Epstein-Barr virus latent membrane protein 1 promotes concentration in multivesicular bodies of fibroblast growth factor 2 and its release through exosomes. Int. J. Cancer 121, 1494-1506. doi: 10.1002/ijc.22844
26. Chen, X., Liang, H., Zhang, J., and Zhang, C. Y. (2013). microRNAs are ligands of Toll-like receptors. RNA 19, 737-739. doi: 10.1261/rna.036319.112
27. Cheung, A. K., Yang, A. K., Ngai, B. H., Yu, S. S., Gao, M., Lau, P. M., et al. (2015). Quantitative detection of eryptosis in human erythrocytes using tunable resistive pulse sensing and annexin-V-beads. Analyst 140, 1337-1348. doi: 10.1039/C4AN02079K
28. Choi, H., Lee, H., Kim, S. R., Gho, Y. S., and Lee, S. K. (2013). Epstein-Barr virus-encoded microRNA BART15-3p promotes cell apoptosis partially by targeting BRUCE. J. Virol. 87, 8135-8144. doi: 10.1128/JVI.03159-12
29. Choudhuri, K., Llodra, J., Roth, E. W., Tsai, J., Gordo, S., Wucherpfennig, K. W., et al. (2014). Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature 507, 118-123. doi: 10.1038/nature12951
30. Chugh, P. E., Sin, S. H., Ozgur, S., Henry, D. H., Menezes, P., Griffith, J., et al. (2013). Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies. PLoS Pathog. 9:e1003484. doi: 10.1371/journal.ppat.1003484
31. Clayton, A., Court, J., Navabi, H., Adams, M., Mason, M. D., Hobot, J. A., et al. (2001). Analysis of antigen presenting cell derived exosomes, based on immune-magnetic isolation and flow cytometry. J. Immunol. Methods 247, 163-174. doi: 10.1016/S0022-1759(00)00321-5
32. Cohen, K. W., Dugast, A. S., Alter, G., McElrath, M. J., and Stamatatos, L. (2015). HIV-1 single-stranded RNA induces CXCL13 secretion in human monocytes via TLR7 activation and plasmacytoid dendritic cell-derived type 1 IFN. J. Immunol. 194, 2769-2775. doi: 10.4049/jimmunol.1400952
33. Colino, J., and Snapper, C. M. (2007). Dendritic cell-derived exosomes express a Streptococcus pneumoniae capsular polysaccharide type 14 cross-reactive antigen that induces protective immunoglobulin responses against pneumococcal infection in mice. Infect. Immun. 75, 220-230. doi: 10.1128/IAI.01217-06
34. Cronemberger-Andrade, A., Aragão-França, L., de Araujo, C. F., Rocha, V. J., Borges-Silva Mda, C., Figueiras, C. P., et al. (2014). Extracellular vesicles from Leishmania-infected macrophages confer an anti-infection cytokine-production profile to naïve macrophages. PLoS Negl. Trop. Dis. 8:e3161. doi: 10.1371/journal.pntd.0003161
35. Cuthbert, J. A. (1990). Hepatitis C. Am. J. Med. Sci. 299, 346-355. doi: 10.1097/00000441-199005000-00010
36. Delabranch, X., Berger, A., Boisrame-Helms, J., and Meziani, F. (2012). Microparticles and infectious diseases. Med. Mal. Infect. 42, 335-343. doi: 10.1016/j.medmal.2012.05.011
37. del Cacho, E., Gallego, M., Lillehoj, H. S., Quilez, J., and Sánchez-Aceso, C. (2013). Tetraspanin-3 regulates protective immunity against Eimeria tenella infection following immunization with dendritic cell-derived exosomes. Vaccine 31, 4668-4674. doi: 10.1016/j.vaccine.2013.06.109
38. Dubuisson, J., Penin, F., and Moradpour, D. (2002). Interaction of hepatitis C virus proteins with host cell membranes and lipids. Trends Cell Biol. 12, 517-523. doi: 10.1016/S0962-8924(02)02383-8
39. Fafi-Kremer, S., Fofana, I., Soulier, E., Carolla, P., Meuleman, P., Leroux-Roels, G., et al. (2010). Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. J. Exp. Med. 207, 2019-2031. doi: 10.1084/jem.20090766
40. Feederle, R., Haar, J., Bernhardt, K., Linnstaedt, S. D., Bannert, H., Lips, H., et al. (2011). The members of an Epstein-Barr virus microRNA cluster cooperate to transform B lymphocytes. J. Virol. 85, 9801-9810. doi: 10.1128/JVI.05100-11
41. Fevrier, B., Vilette, D., Archer, F., Loew, D., Faigle, W., Vidal, M., et al. (2004). Cells release prions in association with exosomes. Proc. Natl. Acad. Sci. U.S.A. 101, 9683-9688. doi: 10.1073/pnas.0308413101
42. Flanagan, J., Middeldorp, J., and Sculley, T. (2003). Localization of the Epstein-Barr virus protein LMP 1 to exosomes. J. Gen. Virol. 84, 1871-1879. doi: 10.1099/vir.0.18944-0
43. Fleming, A., Sampey, G., Chung, M., Bailey, C., van Hoek, M. L., Kashanchi, F., et al. (2014). The carrying pigeons of the cell: exosomes and their role in infectious diseases caused by human pathogens. Pathog. Dis. 71, 109-120. doi: 10.1111/2049-632X.12135
44. Flügel-Koch, C., Ohlmann, A., Piatigorsky, J., and Tamm, E. R. (2002). Disruption of anterior segment development by TGF-β1 overexpression in the eyes of transgenic mice. Dev. Dyn. 225, 111-125. doi: 10.1002/dvdy.10144
45. Fraile-Ramos, A., Pelchen-Matthews, A., Kledal, T. N., Browne, H., Schwartz, T. W., and Marsh, M. (2002). Localization of HCMV UL33 and US27 in endocytic compartments and viral membranes. Traffic 3, 218-232. doi: 10.1034/j.1600-0854.2002.030307.x
46. Gallo, A., Tandon, M., Alevizos, I., and Illei, G. G. (2012). The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS ONE 7:e30679. doi: 10.1371/journal.pone.0030679
47. Gandhi, M. K., Moll, G., Smith, C., Dua, U., Lambley, E., Ramuz, O., et al. (2007). Galectin-1 mediated suppression of Epstein-Barr virus specific T-cell immunity in classic Hodgkin lymphoma. Blood 110, 1326-1329. doi: 10.1182/blood-2007-01-066100
48. Gariano, G. R., Dell'Oste, V., Bronzini, M., Gatti, D., Luganini, A., De Andrea, M., et al. (2012). The intracellular DNA sensor IFI16 gene acts as restriction factor for human Cytomegalovirus replication. PLoS Pathog. 8:e1002498. doi: 10.1371/journal.ppat.1002498
49. Gehrmann, U., Näslund, T. I., Hiltbrunner, S., Larssen, P., and Gabrielsson, S. (2014). Harnessing the exosome-induced immune response for cancer immunotherapy. Semin. Cancer Biol. 28, 58-67. doi: 10.1016/j.semcancer.2014.05.003
50. Ghossoub, R., Lembo, F., Rubio, A., Gaillard, C. B., Bouchet, J., Vitale, N., et al. (2014). Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Nat. Commun. 5:3477. doi: 10.1038/ncomms4477
51. Giri, P. K., Kruh, N. A., Dobos, K. M., and Schorey, J. S. (2010). Proteomic analysis identifies highly antigenic proteins in exosomes from M. tuberculosis-infected and culture filtrate protein-treated macrophages. Proteomics 10, 3190-3202. doi: 10.1002/pmic.200900840
52. Gould, S. J., Booth, A. M., and Hildreth, J. E. (2003). The Trojan exosome hypothesis. Proc. Natl. Acad. Sci. U.S.A. 100, 10592-10597. doi: 10.1073/pnas.1831413100
53. Gourzones, C., Barjon, C., and Busson, P. (2012). Host-tumor interactions in nasopharyngeal carcinomas. Semin. Cancer Biol. 22, 127-136. doi: 10.1016/j.semcancer.2012.01.002
54. Gourzones, C., Ferrand, F. R., Amiel, C., Verillaud, B., Barat, A., Guerin, M., et al. (2013). Consistent high concentration of the viral microRNA BART17 in plasma samples from nasopharyngeal carcinoma patients-evidence of non-exosomal transport. Virol. J. 10, 119. doi: 10.1186/1743-422X-10-119
55. Gourzones, C., Gelin, A., Bombik, I., Klibi, J., Verillaud, B., Guigay, J., et al. (2010). Extra-cellular release and blood diffusion of BART viral microRNAs produced by EBV-infected nasopharyngeal carcinoma cells. Virol. J. 7, 271. doi: 10.1186/1743-422X-7-271
56. Gupta, A., and Pulliam, L. (2014). Exosomes as mediators of neuroinflammation. J. Neuroinflammation 11, 68. doi: 10.1186/1742-2094-11-68
57. Gutierrez-Vazquez, C., Villarroya-Beltri, C., Mittelbrunn, M., and Sanchez-Madrid, F. (2013). Transfer of extracellular vesicles during immune cell-cell interactions. Immunol. Rev. 251, 125-142. doi: 10.1111/imr.12013
58. Gutzeit, C., Nagy, N., Gentile, M., Lyberg, K., Gumz, J., Vallhov, H., et al. (2014). Exosomes derived from Burkitt's lymphoma cell lines induce proliferation, differentiation, and class-switch recombination in B cells. J. Immunol. 192, 5852-5862. doi: 10.4049/jimmunol.1302068
59. Hao, S., Bai, O., Li, F., Yuan, J., Laferte, S., and Xiang, J. (2007). Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumor immunity. Immunology 120, 90-102. doi: 10.1111/j.1365-2567.2006.02483.x
60. Hassani, K., and Olivier, M. (2013). Immunomodulatory impact of Leishmania-induced macrophage exosomes: a comparative proteomic and functional analysis. PLoS Negl. Trop. Dis. 7:e2185. doi: 10.1371/journal.pntd.0002185
61. Haurat, M. F., Elhenawy, W., and Feldman, M. F. (2014). Prokaryotic membrane vesicles: new insights on biogenesis and biological roles. Biol. Chem. 396, 95-109. doi: 10.1515/hsz-2014-0183
62. Henke, j. I., Goergen, D., Zheng, J., Song, Y., Schüttler, C. G., Fehr, C., et al. (2008). microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J. 27, 3300-3310. doi: 10.1038/emboj.2008.244
63. Hotez, P. J., Brindley, P. J., Bethony, J. M., King, C. H., Pearce, E. J., and Jacobson, J. (2008). Helminth infections: the great neglected tropical diseases. J. Clin. Invest. 118, 1311-1321. doi: 10.1172/JCI34261
64. Houali, K., Wang, X., Shimizu, Y., Djennaoui, D., Nicholls, J., Fiorini, S., et al. (2007). A new diagnostic marker for secreted Epstein-Barr virus encoded LMP1 and BARF1 oncoproteins in the serum and saliva of patients with nasopharyngeal carcinoma. Clin. Cancer Res. 13, 4993-5000. doi: 10.1158/1078-0432.CCR-06-2945
65. Hu, G., Gong, A. Y., Roth, A. L., Huang, B. Q., Ward, H. D., Zhu, G., et al. (2013). Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense. PLoS Pathog. 9:e1003261. doi: 10.1371/journal.ppat.1003261
66. Hu, G., Yao, H., Chaudhuri, A. D., Duan, M., Yelamanchili, S. V., Wen, H., et al. (2012). Exosome-mediated shuttling of micro-RNA-29 regulates HIV Tat and morphine-mediated Neuronal dysfunction. Cell Death Dis. 3, e381. doi: 10.1038/cddis.2012.114
67. Huebner, A. R., Somparn, P., Benjachat, T., Leelahvanichkul, A., Avigingsanon, Y., Fenton, R. A., et al. (2015). Exosomes in urine biomarker discovery. Adv. Exp. Med. Biol. 845, 43-58. doi: 10.1007/978-94-017-9523-4_5
68. Husmann, M., Beckmann, E., Boller, K., Kloft, N., Tenzer, S., Bobkiewicz, W., et al. (2009). Elimination of a bacterial pore-forming toxin by sequential endocytosis and exocytosis. FEBS Lett. 583, 337-344. doi: 10.1016/j.febslet.2008.12.028
69. Ishii, N., Funami, K., Tatematsu, M., Seya, T., and Matsumoto, M. (2014). Endosomal localization of TLR8 confers distinctive proteolytic processing on human myeloid cells. J. Immunol. 193, 5118-5128. doi: 10.4049/jimmunol.1401375
70. Jaworski, E., Narayanan, A., Van Duyne, R., Shabbeer-Meyering, S., Iordanskiy, S., Saifuddin, M., et al. (2014a). Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein. J. Biol. Chem. 289, 22284-22305. doi: 10.1074/jbc.M114.549659
71. Jaworski, E., Saifuddin, M., Sampey, G., Shafagati, N., Van Duyne, R., Iordanskiy, S., et al. (2014b). The use of Nanotrap particles technology in capturing HIV-1 virions and viral proteins from infected cells. PLoS ONE 9:e96778. doi: 10.1371/journal.pone.0096778
72. Jiménez-Sousa, M. A., Ralló, N., Berenguer, J., Pineda-Tenor, T., López, J. C., Soriano, V., et al. (2015). TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients. J. Clin. Virol. 65, 62-67. doi: 10.1016/j.jcv.2015.02.004
73. Johnstone, R. M., Adam, M., Hammond, J. R., Orr, L., and Turbide, C. (1987). Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 262, 9412-9420.
74. Jopling, C. L., Yi, M., Lancaster, A. M., Lemon, S. M., and Sarnow, P. (2005). Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309, 1577-1581. doi: 10.1126/science.1113329
75. Kadiu, I., and Gendelman, H. E. (2011a). Human immunodeficiency virus type 1 endocytic trafficking through macrophage bridging conduits facilitates spread of infection. J. Neuroimmune Pharmacol. 6, 658-675. doi: 10.1007/s11481-011-9298-z
76. Kadiu, I., and Gendelman, H. E. (2011b). Macrophage bridging conduit trafficking of HIV-1 through the endoplasmic reticulum and Golgi network. J. Proteome Res. 10, 3225-3238. doi: 10.1021/pr200262q
77. Kadiu, I., Narayanasamy, P., Dash, P. K., Zhang, W., and Gendelman, H. E. (2012). Biochemical and biologic characterization of exosomes and microvesicles as facilitators of HIV-1 infection in macrophages. J. Immunol. 189, 744-754. doi: 10.4049/jimmunol.1102244
78. Kadiu, I., Nowacek, A., McMillan, J., and Gendelman, H. E. (2011). Macrophage endocytic trafficking of antiretroviral nanoparticles. Nanomedicine (Lond.) 6, 975-994. doi: 10.2217/nnm.11.27
79. Kadurugamuwa, J. L., and Beveridge, T. J. (1999). Membrane vesicles derived from Pseudomonas aeruginosa and Shigella flexneri can be integrated into the surfaces of other gram-negative bacteria. Microbiology 145, 2051-2060. doi: 10.1099/13500872-145-8-2051
80. Kalasin, S., and Santore, M. M. (2015). Engineering nanoscale surface features to sustain microparticle rolling flow. ACS Nano 9, 4706-4716. doi: 10.1021/nn505322m
81. Kalra, H., Simpson, R. J., Ji, H., Aikawa, E., Altevogt, P., Askenase, P., et al. (2012). Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 10:e1001450. doi: 10.1371/journal.pbio.1001450
82. Kanwar, S. S., Dunlay, C. J., Simeone, D. M., and Nagrath, S. (2014). Microfluidic device (ExoChip) for On-Chip isolation, quantification and characterization of circulating exosomes. Lab Chip 14, 1891-1900. doi: 10.1039/c4lc00136b
83. Keryer-Bibens, C., Pioche-Durieu, C., Villemant, C., Souquere, S., Nishi, N., Hirashima, M., et al. (2006). Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral latent membrane protein 1 and the immunomodulatory protein galectin 9. BMC Cancer 6:283. doi: 10.1186/1471-2407-6-283
84. Khatua, A. K., Taylor, H. E., Hildreth, J. E., and Popik, W. (2009). Exosomes packaging APOBEC3G confer human immunodeficiency virus resistance to recipient cells. J. Virol. 83, 512-521. doi: 10.1128/JVI.01658-08
85. Khatua, A. K., Taylor, H. E., Hildreth, J. E., and Popik, W. (2010). Inhibition of LINE-1 and Alu retrotransposition by exosomes encapsidating APOBEC3G and APOBEC3F. Virology 400, 68-75. doi: 10.1016/j.virol.2010.01.021
86. Kim, D. K., Kang, B., Kim, O. Y., Choi, D. S., Lee, J., Kim, S. R., et al. (2013). EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. J. Extracell. Vesicles 2, 20384. doi: 10.3402/jev.v2i0.20384
87. Klibi, J., Niki, T., Riedel, A., Pioche-Durieu, C., Souquere, S., Rubinstein, E., et al. (2009). Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells. Blood 113, 1957-1966. doi: 10.1182/blood-2008-02-142596
88. Kooijmans, S. A., Vader, P., van Dommelen, S. M., van Solinge, W. W., and Schiffelers, R. M. (2012). Exosome mimetics: a novel class of drug delivery systems. Int. J. Nanomedicine 7, 1525-1541. doi: 10.2147/IJN.S29661
89. Kulp, A., and Kuehn, M. J. (2010). Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu. Rev. Microbiol. 64, 163-184. doi: 10.1146/annurev.micro.091208.073413
90. Kung, C. P., Meckes, D. G. Jr., and Raab-Traub, N. (2011). Epstein-Barr virus LMP1 activates EGFR, STAT3, and ERK through effects on PKCd. J. Virol. 85, 4399-4408. doi: 10.1128/jvi.01703-10
91. Lagana, A., Russo, F., Veneziano, D., Bella, S. D., Giugno, R., Pulvirenti, A., et al. (2013). Extracellular circulating viral microRNAs: current knowledge and perspectives. Front. Genet. 4:120. doi: 10.3389/fgene.2013.00120
92. Lai, R. C., Yeo, R. W. Y., Tan, K. H., and Lim, S. K. (2013). Exosomes for drug delivery-a novel application for the mesenchymal stem cell. Biotechnol. Adv. 31, 5. doi: 10.1016/j.biotechadv.2012.08.008
93. Leblanc, P., Alais, S., Porto-Carreiro, I., Lehmann, S., Grassi, J., Raposo, G., et al. (2006). Retrovirus infection strongly enhances scrapie infectivity release in cell culture. EMBO J. 25, 2674-2685. doi: 10.1038/sj.emboj.7601162
94. Li, J., Zeng, X. H., Mo, H. Y., Rolen, U., Gao, Y. F., Zhang, X. S., et al. (2007). Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy. PLoS ONE 2:e1122. doi: 10.1371/journal.pone.0001122
95. Liu, Z., Zhang, X., Yu, Q., and He, J. J. (2014). Exosome-associated hepatitis C virus in cell cultures and patient plasma. Biochem. Biophys. Res. Commun. 455, 218-222. doi: 10.1016/j.bbrc.2014.10.146
96. Longatti, A., Boyd, B., and Chisari, F. V. (2014). Virion-independent transfer of replication-competent HCV RNA between permissive cells. J. Virol. 89, 2956-2961. doi: 10.1128/JVI.02721-14
97. Luchini, A., Geho, D. H., Bishop, B., Tran, D., Xia, C., Dufour, R., et al. (2008). Smart hydrogel particles: biomarker harvesting: one-step affinity purification, size exclusion, and protection against degradation. Nano Lett. 8, 350-361. doi: 10.1021/nl072174
98. Luchini, A., Longo, C., Espina, V., Petricoin, E. F. III, and Liotta, L. A. (2009). Nanoparticle technology: addressing the fundamental roadblocks to protein biomarker discovery. J. Mater Chem. 19, 5071-5077. doi: 10.1039/b822264a
99. MacDonald, I. A., and Kuehn, M. J. (2012). Offense and defense: microbial membrane vesicles play both ways. Res. Microbiol. 163, 607-618. doi: 10.1016/j.resmic.2012.10.020
100. Marcilla, A., Martin-Jaular, L., Trelis, M., De Menezes-Neto, A., Osuna, A., Bernal, D., et al. (2014). Extracellular vesicles in parasitic diseases. J. Extracell. Vesicles 3, 25040. doi: 10.3402/jev.v3.25040
101. Marcilla, A., Trelis, M., Cortes, A., Sotillo, J., Cantalapiedra, F., Minguez, M. T., et al. (2012). Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells. PLoS ONE 7:e45974. doi: 10.1371/journal.pone.0045974
102. Marcus, M. E., and Leonard, J. N. (2013). FedExosomes: engineering therapeutic biological nanoparticles that truly deliver. Pharmaceuticals 6, 659-680. doi: 10.3390/ph6050659
103. Masciopinto, F., Giovana, C., Campagmoli, S., Galli-Stampino, L., Colombatto, P., Brunetto, M., et al. (2004). Association of hepatitis C virus envelope proteins with exosomes. Eur. J. Immunol. 34, 2834-2842. doi: 10.1002/eji.200424887
104. Matsumoto, K., Morisaki, T., Kuroki, H., Kubo, M., Onishi, H., Nakamura, K., et al. (2004). Exosomes secreted from monocyte-derived dendritic cells support in vitro naïve CD4+ T cell survival through NF-κB activation. Cell Immunol. 231, 20-29. doi: 10.1016/j.cellimm.2004.11.002
105. McDonald, M. K., Tian, Y., Qureshi, R. A., Gormley, M., Ertel, A., Gao, R., et al. (2014). Functional significance of macrophage-derived exosomes in inflammation and pain. PAIN 155, 1527-1539. doi: 10.1016/j.pain.2014.04.029
106. Meckes, D. G. Jr., Gunawardena, H. P., Dekroon, R. M., Heaton, P. R., Edwards, R. H., Ozgur, S., et al. (2013). Modulation of B-cell exosome proteins by gamma herpesvirus infection. Proc. Natl. Acad. Sci. U.S.A. 110, E2925-E2933. doi: 10.1073/pnas.1303906110
107. Meckes, D. G. Jr., Shair, K. H., Marquitz, A. R., Kung, C. P., Edwards, R. H., and Raab-Traub, N. (2010). Human tumor virus utilizes exosomes for intercellular communication. Proc. Natl. Acad. Sci. U.S.A. 107, 20370-20375. doi: 10.1073/pnas.1014194107
108. Moldovan, L., Batte, K., Wang, Y., Wisler, J., and Piper, M. (2013). Analyzing the circulating microRNAs in exosomes/extracellular vesicles from serum or plasma by qRT-PCR. Methods Mol. Biol. 1024, 129-145. doi: 10.1007/978-1-62703-453-1_10
109. Montaner, S., Galiano, A., Trelis, M., Martin-Jaular, L., Del Portillo, H. A., Bernal, D., et al. (2014). The role of extracellular vesicles in modulating the host immune response during parasitic infections. Front. Immunol. 5:433. doi: 10.3389/fimmu.2014.00433
110. Morales-Sanchez, A., and Fuentes-Panana, E. M. (2014). Human viruses and cancer. Viruses 6, 4047-4079. doi: 10.3390/v6104047
111. Mori, Y., Koike, M., Moriishi, E., Kawabata, A., Tang, H., Oyaizu, H., et al. (2008). Human herpesvirus-6 induces MVB formation, and virus egress occurs by an exosome release pathway. Traffic 9, 1728-1742. doi: 10.1111/j.1600-0854.2008.00796.x
112. Muntasell, A., Berger, A. C., and Roche, P. A. (2007). T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J. 26, 4263-4272. doi: 10.1038/sj.emboj.7601842
113. Nanbo, A., Kawanishi, E., Yoshida, R., and Yoshiyama, H. (2013). Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveola-dependent endocytosis and promote phenotypic modulation in target cells. J. Virol. 87, 10334-10347. doi: 10.1128/JVI.01310-13
114. Narayanan, A., Iordanskiy, S., Das, R., Van Duyne, R., Santos, S., Jaworski, E., et al. (2013). Exosomes derived from HIV-1 infected cells contain trans-activation response element RNA. J. Biol. Chem. 288, 20014-20033. doi: 10.1074/jbc.M112.438895
115. Nieves, W., Petersen, H., Judy, B. M., Blumentritt, C. A., Russel-Lodrigue, K., Roy, C. J., et al. (2014). A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. Clin. Vaccine Immunol. 21, 747-754. doi: 10.1128/CVI.00119-14
116. Nour, A. M., and Modis, Y. (2014). Endosomal Vesicles as vehicles for viral genomes. Trends Cell Biol. 24, 449-454. doi: 10.1016/j.tcb.2014.03.006
117. Okoye, I. S., Coomes, S. M., Pelly, V. S., Czieso, S., Papayannopoulos, V., Tolmachova, T., et al. (2014). MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 41, 89-103. doi: 10.1016/j.immuni.2014.05.019
118. O'Neill, H. C., and Quah, B. J. (2008). Exosomes secreted by bacterially infected macrophages are proinflammatory. Sci. Signal. 1, pe8. doi: 10.1126/stke.16pe8
119. Padgett, D. A., Hotchkiss, A. K., Pyter, L. M., Nelson, R. J., Yang, E., Yeh, P. E., et al. (2004). Epstein-Barr virus-encoded dUTPase modulates immune function and induces sickness behavior in mice. J. Med. Virol. 74, 442-448. doi: 10.1002/jmv.20196
120. Pan, Q., Ramakrishnaiah, V., Henry, S., Fouraschen, S., de Ruiter, P. E., Kwekkeboom, J., et al. (2012). Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interderance (RNAi). Gut 61, 1330-1339. doi: 10.1136/gutjnl-2011-300449
121. Pegtel, D. M., Cosmopoulos, K., Thorley-Lawson, D. A., van Eijndhoven, M. A., Hopmans, E. S., Lindenberg, J. L., et al. (2010). Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. U.S.A. 107, 6328-6333. doi: 10.1073/pnas.0914843107
122. Pegtel, D. M., van de Garde, M. D., and Middeldorp, J. M. (2011). Viral miRNAs exploiting the endosomal-exosomal pathway for intercellular cross-talk and immune evasion. Biochim. Biophys. Acta 1809, 715-721. doi: 10.1016/j.bbagrm.2011.08.002
123. Pierson, T., Matrakas, D., Taylor, Y. U., Manyam, G., Morozov, V. N., Zhou, W., et al. (2011). Proteomic characterization and functional analysis of outer membrane vesicles of Francisella novicida suggests possible role in virulence and use as a vaccine. J. Proteome Res. 10, 954-967. doi: 10.1021/pr1009756
124. Piper, R. C., and Katzmann, D. J. (2007). Biogenesis and function of multivesicular bodies. Annu. Rev. Cell Dev. Biol. 23, 519-547. doi: 10.1146/annurev.cellbio.23.090506.123319
125. Pitt, J. M., Charrier, M., Viaud, S., André, F., Besse, B., Chaput, N., et al. (2014). Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. J. Immunol. 193, 1006-1011. doi: 10.4049/jimmunol.1400703
126. Prichard, R. K., Basáñez, M. G., Boatin, B. A., McCarthy, J. S., Garvía, H. H., Yang, G. J., et al. (2012). A research agenda for helminth diseases of humans: intervention for control and elimination. PLoS Negl. Trop. Dis. 6:e1549. doi: 10.1371/journal.pntd.0001549
127. Quah, B. J. C., and O'Neill, H. C. (2007). Mycoplasma contaminants present in exosome preparations induce polyclonal B cell responses. J. Leukoc. Biol. 82, 1070-1082. doi: 10.1189/jlb.0507277
128. Raimondo, S., Saieva, L., Corrado, C., Fontana, S., Flugy, A., Rizzo, A., et al. (2015). Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun Signal. 13, 8. doi: 10.1186/s12964-015-0086-x
129. Ramakrishnaiah, V., Thumann, C., Fofana, I., Habersetzer, F., Pan, Q., de Ruiter, P. E., et al. (2013). Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc. Natl. Acad. Sci. U.S.A. 110, 13109-13113. doi: 10.1073/pnas.1221899110
130. Roberts, J. A., Thorley, B. R., Bruggink, L. D., and Marshall, J. A. (2012). Electron microscope detection of endogenous infection of retrovirus-like particles I nL20B cells. Microscopy 62, 485-486. doi: 10.1093/jmicro/dfs133
131. Roy, P., Periasamy, A. P., Lin, C. Y., Her, G. M., Chiu, W. J., Li, C. L., et al. (2015). Photoluminescent graphene quantum dots for in vivo imaging of apoptotic cells. Nanoscale. 7, 2504-2510. doi: 10.1039/C4NR07005D
132. Saá, P., Yakovleva, O., de Castro, J., Vasilyeva, I., De Paoli, S. H., Simak, J., et al. (2014). First demonstration of transmissible spongiform encephalopathy-associated prion protein (PrPTSE) in extracellular vesicles from plasma of mice infected with mouse-adapted variant Creutzfeldt-Jakob disease by in vitro amplification. J. Biol. Chem. 289, 29247-29260. doi: 10.1074/jbc.M114.589564
133. Sampey, G. C., Meyering, S. S., Asad Zadeh, M., Saifuddin, M., Hakami, R. M., and Kashanchi, F. (2014). Exosomes and their role in CAN viral infections. J. Neurovirol. 20, 199-208. doi: 10.1007/s13365-014-0238-6
134. Schnitzer, J. K., Berzel, S., Fajardo-Moser, M., Remer, K. A., and Moll, H. (2010). Fragments of antigen-loaded dendritic cells (DC) and DC-derived exosomes induce protective immunity against Leishmania major. Vaccine 28, 5785-5793. doi: 10.1016/j.vaccine.2010.06.077
135. Schorey, J. S., and Bhatnagar, S. (2008). Exosome function: from tumor immunology to pathogen biology. Traffic 9, 871-881. doi: 10.1111/j.1600-0854.2008.00734.x
136. Shafagati, N., Narayann, A., Baer, A., Fite, K., Pinkham, C., Bailey, C., et al. (2013). The use of nanotrap particles as a sample enrichment method to enhance the Detection of Rift Vally Fever Virus. PLoS Negl. Trop. Dis. 7:e2296. doi: 10.1371/journal.pntd.0002296
137. Shair, K. H., Schnegg, C. I., and Raab-Traub, N. (2009). Epstein-Barr virus latent membrane protein-1 effects on junctional plakoglobin and induction of a cadherin switch. Cancer Res. 69, 5734-5742. doi: 10.1158/0008-5472.CAN-09-0468
138. Singh, P. P., LeMaire, C., Tan, J. C., Zeng, E., and Schorey, J. S. (2011). Exosomes released from M. tuberculosis infected cells can suppress IFN-γ mediated activation of naïve macrophages. PLoS ONE 6:e18564. doi: 10.1371/journal.pone.0018564
139. Singh, P. P., Smith, V. L., Karakousis, P. C., and Schorey, J. S. (2012). Exosomes isolated from mycobacteria-infected mice or cultured macrophages can recruit and activate immune cells in vitro and in vivo. J. Immunol. 189, 777-785. doi: 10.4049/jimmunol.1103638
140. Singh, V. V., Kerur, N., Bottero, V., Dutta, S., Chakraborty, S., Ansari, M. A., et al. (2013). Kaposi's sarcoma-associated herpesvirus latency in endothelial and B cells activates gamma interferon-inducible protein 16-mediated inflammasomes. J. Virol. 87, 4417-4431. doi: 10.1128/JVI.03282-12
141. Subra, C., Grand, D., Laulagnier, K., Stella, A., Lambeau, G., Paillasse, M., et al. (2010). Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J. Lipid Res. 51, 2105-2120. doi: 10.1194/jlr.M003657
142. Sun, D., Zhuang, X., Xiang, X., Liu, Y., Zhang, S., Liu, C., et al. (2010). A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol. Ther. 18, 1606-1614. doi: 10.1038/mt.2010.105
143. Tamai, K., Shiina, M., Tanaka, N., Nakano, T., Yamamoto, A., Kondo, Y., et al. (2012). Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway. Virology 422, 377-385. doi: 10.1016/j.virol.2011.11.009
144. Temme, S., Eis-Hübinger, A. M., McLellan, A. D., and Koch, N. (2010). The herpes simplex virus-1 encoded glycoprotein B diverts HLA-DR into the exosome pathway. J. Immunol. 184, 236-243. doi: 10.4049/jimmunol.0902192
145. Thery, C., Amigorena, S., Raposo, G., and Clayton, A. (2006). Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. Chap. 3, Unit 3.22. doi: 10.1002/0471143030.cb0322s30
146. Thery, C., Duban, L., Segura, E., Veron, P., Lantz, O., and Amigorena, S. (2002). Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes. Nat. Immunol. 3, 1156-1162. doi: 10.1038/ni854
147. Tran, T., Mattheolabakis, G., Aldawsari, H., and Amiji, M. (2015). Exosomes as nanocarriers for immunotherapy of cancers and inflammatory diseases. Clin. Immunol. 160, 46-58. doi: 10.1016/j.clim.2015.03.021
148. Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., and Lötvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654-659. doi: 10.1038/ncb1596
149. Vallhov, H., Gutzeit, C., Johansson, S. M., Nagy, N., Paul, M., Li, Q., et al. (2010). Exosomes containing glycoprotein 350 released by EBV-transformed B cells selectively target B cells through CD21 and block EBV infection in vitro. J. Immunol. 186, 73-82. doi: 10.4049/jimmunol.1001145
150. Vereide, D. T., Seto, E., Chiu, Y. F., Hayes, M., Tagawa, T., Grundhoff, A., et al. (2014). Epstein-Barr virus maintains lymphomas via its miRNAs. Oncogene 33, 1258-1264. doi: 10.1038/onc.2013.71
151. Verweij, F. J., van Eijndhoven, M. A., Hopmans, E. S., Vendrig, T., Wurdinger, T., Cahir-McFarland, E., et al. (2011). LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation. EMBO J. 30, 2115-2129. doi: 10.1038/emboj.2011.123
152. Verweij, F. J., van Eijndhoven, M. A., Middeldorp, J., and Pegtel, D. M. (2013). Analysis of viral microRNA exchange via exosomes in vitro and in vivo. Methods Mol. Biol. 1024, 53-68. doi: 10.1007/978-1-62703-453-1_5
153. Wang, D., and Sun, W. (2014). Urinary extracellular microvesicles: isolation methods and prospects for urinary proteome. Proteomics 14, 1922-1932. doi: 10.1002/pmic.201300371
154. Wang, F., Gregory, C., Sample, C., Rowe, M., Liebowitz, D., Murray, R., et al. (1990). Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J. Virol. 64, 2309-2318.
155. Wang, Y., Wang, G., Wang, Z., Zhang, H., Zhang, L., and Cheng, Z. (2014). Chicken biliary exosomes enhance CD4+ T cell proliferation and inhibit ALV-J replication in liver. Biochem. Cell Biol. 92, 145-151. doi: 10.1139/bcb-2013-0096
156. Wilson, J. A., Zhang, D., Huys, A., and Richardson, C. D. (2011). Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation. J. Virol. 85, 2342-2350. doi: 10.1128/JVI.02046-10
157. Winkler, C. W., Taylor, K. G., and Peterson, K. E. (2014). Location is everything: let-7b microRNA and TLR7 signaling results in a painful TRP. Sci. Signal. 7, pe14. doi: 10.1126/scisignal.2005407
158. Wong, S. H., Lennon, D. R., Jackson, C. M., Stewart, J. M., Reid, S., Ypma, E., et al. (2009). Immunogenicity and tolerability in infants of a New Zealand epidemic strain meningococcal B outer membrane vesicle vaccine. Pediatr. Infect. Dis. J. 28, 385-390. doi: 10.1097/INF.0b013e318195205e
159. Wurdinger, T., Gatson, N. N., Balaj, L., Kaur, B., Breakefield, X. O., and Pegtel, D. M. (2012). Extracellular vesicles and their convergence with viral pathways. Adv. Virol. 2012, 767694. doi: 10.1155/2012/767694
160. Yang, C., Chalasani, G., Ng, Y.-H., and Robbins, P. D. (2012a). Exosomes released from Mycoplasma infected tumor cells activate inhibitory B cells. PLoS ONE 7:e36138. doi: 10.1371/journal.pone.0036138
161. Yang, C., Ruffner, M. A., Kim, S., and Robbins, P. D. (2012b). Plasma-derived MHC II+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses. Eur. J. Immunol. 42, 1778-1784. doi: 10.1002/eji.201141978
162. Yang, C., and Robbins, P. D. (2012). Immunosuppressive exosomes: a new approach for treating arthritis. Int. J. Rheumatol. 2012, 573528. doi: 10.1155/2012/573528
163. Yoshizaki, T., Kondo, S., Wakisaka, N., Murono, S., Endo, K., Sugimoto, H., et al. (2013). Pathogenic role of Epstein-Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma. Cancer Lett. 337, 1-7. doi: 10.1016/j.canlet.2013.05.018
164. Zheng, X., Chen, F., Zhang, J., Zhang, Q., and Lin, J. (2014). Exosome analysis: a promising biomarker system with special attention to saliva. J. Membr. Biol. 247, 1129-1136. doi: 10.1007/s00232-014-9717-1
165. Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R. C., et al. (2011). Treatment of brain inflammatory diseases by delivering exosomes encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol. Ther. 19, 1769-1779.
166. Zwickl, H., Traxler, E., Staettner, S., Parzefall, W., Grasl-Kraupp, B., Karner, J., et al. (2005). A novel technique to specifically analyze the secretome of cells and tissues. Electrophoresis 26, 2779-2785. doi: 10.1002/elps.200410387