A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions
Abstract
:1. Introduction
2. Extracellular Vesicles Overview
3. Molecular Structure of Exosomes
4. Exosomes Biogenesis and Their Role in the Immune Response to Viral Infection
5. Exosomes Purification and Characterization
5.1. Ultracentrifugation Techniques
5.2. Polymer Precipitation
5.3. Size-Based Isolation Techniques
5.4. Immunoaffinity Chromatography (IAC)
6. Exosomal Pathway and Viral Pathogenesis
6.1. Viruses Hijack the Exosomal Machinery System (ESCRT and Rab GTPases)
6.2. Signatures of Different Viruses in Exosomes and Their Role as Vehicles for Viral Elements
6.3. Role of Exosomes as Potential Mediators in Viral Pathogenesis
7. Exosomes as a Potent Therapy in Viral Infections
8. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
- Sedgwick, A.E.; D’Souza-Schorey, C. The biology of extracellular microvesicles. Traffic 2018, 19, 319–327. [Google Scholar] [CrossRef]
- Van Niel, G.; D’Angelo, G.; Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 2018, 19, 213–228. [Google Scholar] [CrossRef]
- Zaborowski, M.P.; Balaj, L.; Breakefield, X.O.; Lai, C.P. Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study. Bioscience 2015, 65, 783–797. [Google Scholar] [CrossRef] [Green Version]
- Kalra, H.; Drummen, G.P.C.; Mathivanan, S. Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int. J. Mol. Sci. 2016, 17, 170. [Google Scholar] [CrossRef] [Green Version]
- György, B.; Szabó, T.G.; Pásztói, M.; Pál, Z.; Misják, P.; Aradi, B.; László, V.; Pállinger, É.; Pap, E.; Kittel, Á.; et al. Membrane vesicles, current state-of-the-art: Emerging role of extracellular vesicles. Cell. Mol. Life Sci. 2011, 68, 2667–2688. [Google Scholar] [CrossRef] [Green Version]
- Yuana, Y.; Sturk, A.; Nieuwland, R. Extracellular vesicles in physiological and pathological conditions. Blood Rev. 2013, 27, 31–39. [Google Scholar] [CrossRef] [Green Version]
- Robbins, P.D.; Morelli, A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 2014, 14, 195–208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frühbeis, C.; Fröhlich, D.; Kuo, W.P.; Amphornrat, J.; Thilemann, S.; Saab, A.S.; Kirchhoff, F.; Möbius, W.; Goebbels, S.; Nave, K.-A.; et al. Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication. PLoS Biol. 2013, 11, e1001604. [Google Scholar] [CrossRef] [Green Version]
- Holm, M.M.; Kaiser, J.; Schwab, M.E. Extracellular Vesicles: Multimodal Envoys in Neural Maintenance and Repair. Trends Neurosci. 2018, 41, 360–372. [Google Scholar] [CrossRef]
- Silverman, J.M.; Reiner, N.E. Exosomes and other microvesicles in infection biology: Organelles with unanticipated phenotypes. Cell. Microbiol. 2010, 13, 1–9. [Google Scholar] [CrossRef]
- Schorey, J.S.; Cheng, Y.; Singh, P.P.; Smith, V.L. Exosomes and other extracellular vesicles in host–pathogen interactions. EMBO Rep. 2015, 16, 24–43. [Google Scholar] [CrossRef] [Green Version]
- Nogués, L.; Benito-Martin, M.; Hergueta-Redondo, M.; Peinado, H. The influence of tumour-derived extracellular vesicles on local and distal metastatic dissemination. Mol. Asp. Med. 2018, 60, 15–26. [Google Scholar] [CrossRef]
- Xu, R.; Rai, A.; Chen, M.; Suwakulsiri, W.; Greening, D.; Simpson, R. Extracellular vesicles in cancer—Implications for future improvements in cancer care. Nat. Rev. Clin. Oncol. 2018, 15, 617–638. [Google Scholar] [CrossRef]
- Kouwaki, T.; Fukushima, Y.; Daito, T.; Sanada, T.; Yamamoto, N.; Mifsud, E.J.; Leong, C.R.; Tsukiyama-Kohara, K.; Kohara, M.; Matsumoto, M.; et al. Extracellular Vesicles Including Exosomes Regulate Innate Immune Responses to Hepatitis B Virus Infection. Front. Immunol. 2016, 7, 335. [Google Scholar] [CrossRef] [Green Version]
- Meckes, D.G.; Raab-Traub, N. Microvesicles and Viral Infection. J. Virol. 2011, 85, 12844–12854. [Google Scholar] [CrossRef] [Green Version]
- Altan-Bonnet, N. Extracellular vesicles are the Trojan horses of viral infection. Curr. Opin. Microbiol. 2016, 32, 77–81. [Google Scholar] [CrossRef] [Green Version]
- Anderson, M.R.; Kashanchi, F.; Jacobson, S. Exosomes in Viral Disease. Neurotherapeuthics 2016, 13, 535–546. [Google Scholar] [CrossRef]
- Meckes, D.G. Exosomal Communication Goes Viral. J. Virol. 2015, 89, 5200–5203. [Google Scholar] [CrossRef] [Green Version]
- Nolte, E.; Hoen, T.; Cremer, T.; Gallo, R.C.; Margolis, L.B. Extracellular vesicles and viruses: Are they close relatives. Proc. Natl. Acad. Sci. USA 2016, 113, 9155–9161. [Google Scholar] [CrossRef] [Green Version]
- Mitchell, P.; Petfalski, E.; Shevchenko, A.; Mann, M.; Tollervey, D. The exosome: A conserved eukaryotic RNA processing complex containing multiple 3′→ 5′ exoribonucleases. Cell 1997, 91, 457–466. [Google Scholar] [CrossRef] [Green Version]
- Colombo, M.; Moita, C.; van Niel, G.; Kowal, J.; Vigneron, J.; Benaroch, P.; Manel, N.; Moita, L.F.; Théry, C.; Raposo, G. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 2013, 126, 5553–5565. [Google Scholar] [CrossRef] [Green Version]
- Théry, C.; Zitvogel, L.; Amigorena, S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2, 569–579. [Google Scholar] [CrossRef]
- Pan, B.-T.; Johnstone, R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell 1983, 33, 967–978. [Google Scholar] [CrossRef]
- Johnstone, R.M.; Adam, M.; Hammond, J.R.; Orr, L.; Turbide, C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 1987, 262, 9412–9420. [Google Scholar] [CrossRef]
- Akers, J.C.; Gonda, D.; Kim, R.; Carter, B.S.; Chen, C.C. Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neuro Oncol. 2013, 113, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750. [Google Scholar] [CrossRef] [Green Version]
- Doyle, L.M.; Wang, M.Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 2019, 8, 727. [Google Scholar] [CrossRef] [Green Version]
- Dang, V.D.; Jella, K.K.; Ragheb, R.R.T.; Denslow, N.D.; Alli, A.A. Lipidomic and proteomic analysis of exosomes from mouse cortical collecting duct cells. FASEB J. 2017, 31, 5399–5408. [Google Scholar] [CrossRef] [Green Version]
- Ridder, K.; Keller, S.; Dams, M.; Rupp, A.-K.; Schlaudraff, J.; Del Turco, D.; Starmann, J.; Macas, J.; Karpova, D.; Devraj, K.; et al. Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation. PLoS Biol. 2014, 12, e1001874. [Google Scholar] [CrossRef]
- Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol. 2007, 35, 495–516. [Google Scholar] [CrossRef]
- Kerr, J.F.R.; Wyllie, A.H.; Currie, A. A basic biological phenomenon with wideranging implications in tissue kinetics. Br. J. Cancer 1972, 26, 239. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bao, Q.; Shi, Y. Apoptosome: A platform for the activation of initiator caspases. Cell Death Differ. 2007, 14, 56–65. [Google Scholar] [CrossRef]
- Cocucci, E.; Racchetti, G.; Meldolesi, J. Shedding microvesicles: Artefacts no more. Trends Cell Biol. 2009, 19, 43–51. [Google Scholar] [CrossRef] [PubMed]
- Van der Pol, E.; Böing, A.N.; Harrison, P.; Sturk, A.; Nieuwland, R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol. Rev. 2012, 64, 676–705. [Google Scholar] [CrossRef] [Green Version]
- Smolarz, M.; Pietrowska, M.; Matysiak, N.; Mielańczyk, Ł.; Widłak, P. Proteome Profiling of Exosomes Purified from a Small Amount of Human Serum: The Problem of Co-Purified Serum Components. Proteomes 2019, 7, 18. [Google Scholar] [CrossRef] [Green Version]
- De Toro, J.; Herschlik, L.; Waldner, C.; Mongini, C. Emerging Roles of Exosomes in Normal and Pathological Conditions: New Insights for Diagnosis and Therapeutic Applications. Front. Immunol. 2015, 6, 203. [Google Scholar] [CrossRef] [Green Version]
- Lässer, C.; Alikhani, V.S.; Ekström, K.; Eldh, M.; Paredes, P.T.; Bossios, A.; Sjöstrand, M.; Gabrielsson, S.; Lötvall, J.; Valadi, H. Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages. J. Transl. Med. 2011, 9, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Street, J.M.; Barran, P.E.; Mackay, C.L.; Weidt, S.; Balmforth, C.; Walsh, T.S.; Chalmers, R.T.A.; Webb, D.J.; Dear, J.W. Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J. Transl. Med. 2012, 10, 5. [Google Scholar] [CrossRef] [Green Version]
- Madison, M.N.; Roller, R.J.; Okeoma, C.M. Human semen contains exosomes with potent anti-HIV-1 activity. Retrovirology 2014, 11, 1–16. [Google Scholar] [CrossRef] [Green Version]
- Villanueva, M.T. Microenvironment: Small containers, important cargo. Nat. Rev. Cancer 2014, 14, 764. [Google Scholar] [CrossRef]
- Pant, S.; Hilton, H.; Burczynski, M.E. The multifaceted exosome: Biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem. Pharmacol. 2012, 83, 1484–1494. [Google Scholar] [CrossRef] [PubMed]
- Hurley, J.H.; Odorizzi, G. Get on the exosome bus with ALIX. Nat. Cell Biol. 2012, 14, 654–655. [Google Scholar] [CrossRef]
- Stoorvogel, W. Resolving sorting mechanisms into exosomes. Cell Res. 2015, 25, 531–532. [Google Scholar] [CrossRef] [Green Version]
- Bowden, T.J.; Kraev, I.; Lange, S. Extracellular Vesicles and Post-Translational Protein Deimination Signatures in Mollusca—The Blue Mussel (Mytilus edulis), Soft Shell Clam (Mya arenaria), Eastern Oyster (Crassostrea virginica) and Atlantic Jacknife Clam (Ensis leei). Biology 2020, 9, 416. [Google Scholar] [CrossRef]
- Bowden, T.J.; Kraev, I.; Lange, S. Extracellular vesicles and post-translational protein deimination signatures in haemolymph of the American lobster (Homarus americanus). Fish Shellfish. Immunol. 2020, 106, 79–102. [Google Scholar] [CrossRef] [PubMed]
- Azmi, A.S.; Bao, B.; Sarkar, F.H. Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer Metastasis Rev. 2013, 32, 623–642. [Google Scholar] [CrossRef] [Green Version]
- Beckler, M.D.; Higginbotham, J.N.; Franklin, J.L.; Ham, A.-J.; Halvey, P.J.; Imasuen, I.E.; Whitwell, C.; Li, M.; Liebler, D.; Coffey, R.J. Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS. Mol. Cell. Proteom. 2013, 12, 343–355. [Google Scholar] [CrossRef] [Green Version]
- Kosaka, N. Decoding the Secret of Cancer by Means of Extracellular Vesicles. J. Clin. Med. 2016, 5, 22. [Google Scholar] [CrossRef]
- Takahashi, K.; Yan, I.K.; Wood, J.; Haga, H.; Patel, T. Involvement of Extracellular Vesicle Long Noncoding RNA (linc-VLDLR) in Tumor Cell Responses to Chemotherapy. Mol. Cancer Res. 2014, 12, 1377–1387. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chaput, N.; Taïeb, J.; André, F.; Zitvogel, L. The potential of exosomes in immunotherapy. Expert Opin. Biol. Ther. 2005, 5, 737–747. [Google Scholar] [CrossRef]
- Li, S.; Li, S.; Wu, S.; Chen, L. Exosomes Modulate the Viral Replication and Host Immune Responses in HBV Infection. Biomed. Res. Int. 2019, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Longatti, A.; Boyd, B.; Chisari, F.V. Virion-Independent Transfer of Replication-Competent Hepatitis C Virus RNA between Permissive Cells. J. Virol. 2015, 89, 2956–2961. [Google Scholar] [CrossRef] [Green Version]
- Théry, C.; Ostrowski, M.; Segura, E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 2009, 9, 581–593. [Google Scholar] [CrossRef] [PubMed]
- Mathivanan, S.; Lim, J.W.E.; Tauro, B.J.; Ji, H.; Moritz, R.L.; Simpson, R.J. Proteomics Analysis of A33 Immunoaffinity-purified Exosomes Released from the Human Colon Tumor Cell Line LIM1215 Reveals a Tissue-specific Protein Signature. Mol. Cell. Proteom. 2010, 9, 197–208. [Google Scholar] [CrossRef] [Green Version]
- Van Niel, G.; Porto-Carreiro, I.; Simoes, S.; Raposo, G. Exosomes: A Common Pathway for a Specialized Function. J. Biochem. 2006, 140, 13–21. [Google Scholar] [CrossRef]
- Lydic, T.A.; Townsend, S.; Adda, C.G.; Collins, C.; Mathivanan, S.; Reid, G.E. Rapid and comprehensive ‘shotgun’ lipidome profiling of colorectal cancer cell derived exosomes. Methods 2015, 87, 83–95. [Google Scholar] [CrossRef] [Green Version]
- Subra, C.; Laulagnier, K.; Perret, B.; Record, M. Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 2007, 89, 205–212. [Google Scholar] [CrossRef] [PubMed]
- Brouwers, J.F.; Aalberts, M.; Jansen, J.W.A.; Van Niel, G.; Wauben, M.; Stout, T.A.E.; Helms, J.B.; Stoorvogel, W. Distinct lipid compositions of two types of human prostasomes. Proteomics 2013, 13, 1660–1666. [Google Scholar] [CrossRef]
- Matsuo, H.; Chevallier, J.; Mayran, N.; Le Blanc, I.; Ferguson, C.; Fauré, J.; Blanc, N.S.; Matile, S.; Dubochet, J.; Sadoul, R.; et al. Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization. Science 2004, 303, 531–534. [Google Scholar] [CrossRef]
- Subra, C.; Grand, D.; Laulagnier, K.; Stella, A.; Lambeau, G.; Paillasse, M.; De Medina, P.; Monsarrat, B.; Perret, B.; Silvente-Poirot, S.; et al. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J. Lipid Res. 2010, 51, 2105–2120. [Google Scholar] [CrossRef] [Green Version]
- Conde-Vancells, J.; Rodriguez-Suarez, E.; Embade, N.; Gil, D.; Matthiesen, R.; Valle, M.; Elortza, F.; Lu, S.C.; Mato, J.M.; Falcon-Perez, J.M. Characterization and Comprehensive Proteome Profiling of Exosomes Secreted by Hepatocytes. J. Proteome Res. 2008, 7, 5157–5166. [Google Scholar] [CrossRef] [Green Version]
- Batista, B.S.; Eng, W.S.; Pilobello, K.T.; Hendricks-Muñoz, K.D.; Mahal, L.K. Identification of a Conserved Glycan Signature for Microvesicles. J. Proteome Res. 2011, 10, 4624–4633. [Google Scholar] [CrossRef] [Green Version]
- Saunderson, S.; Dunn, A.C.; Crocker, P.; McLellan, A.D. CD169 mediates the capture of exosomes in spleen and lymph node. Blood J. Am. Soc. Hematol. 2014, 123, 208–216. [Google Scholar] [CrossRef]
- Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9, 654–659. [Google Scholar] [CrossRef] [Green Version]
- Schorey, J.S.; Bhatnagar, S. Exosome Function: From Tumor Immunology to Pathogen Biology. Traffic 2008, 9, 871–881. [Google Scholar] [CrossRef] [Green Version]
- Bhatnagar, S.; Shinagawa, K.; Castellino, F.J.; Schorey, J.S. Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 2007, 110, 3234–3244. [Google Scholar] [CrossRef] [Green Version]
- McAndrews, K.M.; Kalluri, R. Mechanisms associated with biogenesis of exosomes in cancer. Mol. Cancer 2019, 18, 1–11. [Google Scholar] [CrossRef]
- Williams, R.L.; Urbé, S. The emerging shape of the ESCRT machinery. Nat. Rev. Mol. Cell Biol. 2007, 8, 355–368. [Google Scholar] [CrossRef] [PubMed]
- Kennedy, M.J.; Ehlers, M.D. Mechanisms and function of dendritic exocytosis. Neuron 2011, 69, 856–875. [Google Scholar] [CrossRef] [Green Version]
- Mashouri, L.; Yousefi, H.; Aref, A.R.; Ahadi, A.M.; Molaei, F.; Alahari, S.K. Exosomes: Composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol. Cancer 2019, 18, 1–14. [Google Scholar] [CrossRef]
- Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science 2020, 367, 6478. [Google Scholar] [CrossRef]
- Juan, T.; Fürthauer, M. Biogenesis and function of ESCRT-dependent extracellular vesicles. Semin. Cell Dev. Biol. 2018, 74, 66–77. [Google Scholar] [CrossRef]
- Babst, M. MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between. Curr. Opin. Cell Biol. 2011, 23, 452–457. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Janas, T.; Janas, M.M.; Sapoń, K.; Janas, T. Mechanisms of RNA loading into exosomes. FEBS Lett. 2015, 589, 1391–1398. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Izquierdo-Useros, N.; Lorizate, M.; Puertas, M.C.; Rodriguez-Plata, M.T.; Zangger, N.; Erikson, E.; Pino, M.; Erkizia, I.; Glass, B.; Clotet, B.; et al. Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection through Recognition of Viral Membrane Gangliosides. PLoS Biol. 2012, 10, e1001448. [Google Scholar] [CrossRef] [PubMed]
- Van Dongen, H.M.; Masoumi, N.; Witwer, K.W.; Pegtel, D.M. Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery. Microbiol. Mol. Biol. Rev. 2016, 80, 369–386. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Bergelson, J.M. Adenovirus receptors. J. Virol. 2005, 79, 12125–12131. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheruiyot, C.; Pataki, Z.; Ramratnam, B.; Li, M. Proteomic Analysis of Exosomes and Its Application in HIV-1 Infection. Proteomics Clin. Appl. 2018, 12, 1–6. [Google Scholar] [CrossRef]
- Thery, C.; Boussac, M.; Veron, P.; Ricciardi-Castagnoli, P.; Raposo, G.; Garin, J.; Amigorena, S. Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 2001, 166, 7309–7318. [Google Scholar] [CrossRef] [Green Version]
- Alenquer, M.; Amorim, M.J. Exosome Biogenesis, Regulation, and Function in Viral Infection. Viruses 2015, 7, 5066–5083. [Google Scholar] [CrossRef] [Green Version]
- Temme, S.; Eis-Hübinger, A.M.; McLellan, A.D.; Koch, N. The Herpes Simplex Virus-1 Encoded Glycoprotein B Diverts HLA-DR into the Exosome Pathway. J. Immunol. 2010, 184, 236–243. [Google Scholar] [CrossRef] [Green Version]
- Abels, E.R.; Breakefield, X.O. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake; Springer: Berlin/Heidelberg, Germany, 2016. [Google Scholar]
- Kalamvoki, M.; Du, T.; Roizman, B. Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs. Proc. Natl. Acad. Sci. USA 2014, 111, E4991–E4996. [Google Scholar] [CrossRef] [Green Version]
- Pleet, M.L.; Mathiesen, A.; DeMarino, C.; Akpamagbo, Y.A.; Barclay, R.A.; Schwab, A.; Iordanskiy, S.; Sampey, G.C.; Lepene, B.; Ilinykh, P.A.; et al. Corrigendum: Ebola VP40 in exosomes can cause immune cell dysfunction. Front. Microbiol. 2018, 9, 692. [Google Scholar] [CrossRef] [Green Version]
- Pleet, M.L.; Erickson, J.; DeMarino, C.; Barclay, R.A.; Cowen, M.; Lepene, B.; Liang, J.; Kuhn, J.H.; Prugar, L.; Stonier, S.W.; et al. Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles. J. Infect. Dis. 2018, 218, S365–S387. [Google Scholar] [CrossRef]
- Pegtel, D.M.; Cosmopoulos, K.; Thorley-Lawson, D.A.; van Eijndhoven, M.A.J.; Hopmans, E.S.; Lindenberg, J.L.; de Gruijl, T.D.; Würdinger, T.; Middeldorp, J.M. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. USA 2010, 107, 6328–6333. [Google Scholar] [CrossRef] [Green Version]
- Ahmed, W.; Philip, P.S.; Attoub, S.; Khan, G. Epstein–Barr virus-infected cells release Fas ligand in exosomal fractions and induce apoptosis in recipient cells via the extrinsic pathway. J. Gen. Virol. 2015, 96, 3646–3659. [Google Scholar] [CrossRef]
- Vallhov, H.; Gutzeit, C.; Johansson, S.M.; Nagy, N.; Paul, M.; Li, Q.; Friend, S.; George, T.C.; Klein, E.; Scheynius, A.; et al. Exosomes containing glycoprotein 350 released by EBV-transformed B cells selectively target B cells through CD21 and block EBV infection in vitro. J. Immunol. 2011, 186, 73–82. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ikeda, M.; Longnecker, R. Cholesterol is critical for Epstein-Barr virus latent membrane protein 2A trafficking and protein stability. Virology 2007, 360, 461–468. [Google Scholar] [CrossRef] [PubMed]
- Flanagan, J.; Middeldorp, J.; Sculley, T. Localization of the Epstein–Barr virus protein LMP 1 to exosomes. J. Gen. Virol. 2003, 84, 1871–1879. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, W.; Philip, P.S.; Tariq, S.; Khan, G. Epstein-Barr Virus-Encoded Small RNAs (EBERs) Are Present in Fractions Related to Exosomes Released by EBV-Transformed Cells. PLoS ONE 2014, 9, e99163. [Google Scholar] [CrossRef]
- Ramakrishnaiah, V.; Thumann, C.; Fofana, I.; Habersetzer, F.; Pan, Q.; de Ruiter, P.E.; Willemsen, R.; Demmers, J.A.A.; Raj, V.S.; Jenster, G.; et al. Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc. Natl. Acad. Sci. USA 2013, 110, 13109–13113. [Google Scholar] [CrossRef] [Green Version]
- Bukong, T.N.; Momen-Heravi, F.; Kodys, K.; Bala, S.; Szabo, G. Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90. PLOS Pathog. 2014, 10, e1004424. [Google Scholar] [CrossRef] [Green Version]
- Dreux, M.; Garaigorta, U.; Boyd, B.; Décembre, E.; Chung, J.; Whitten-Bauer, C.; Wieland, S.; Chisari, F.V. Short-Range Exosomal Transfer of Viral RNA from Infected Cells to Plasmacytoid Dendritic Cells Triggers Innate Immunity. Cell Host Microbe 2012, 12, 558–570. [Google Scholar] [CrossRef] [Green Version]
- Zhu, X.; He, Z.; Yuan, J.; Wen, W.; Huang, X.; Hu, Y.; Lin, C.; Pan, J.; Li, R.; Deng, H.; et al. IFITM3-containing exosome as a novel mediator for anti-viral response in dengue virus infection. Cell. Microbiol. 2015, 17, 105–118. [Google Scholar] [CrossRef]
- Honegger, A.; Schilling, D.; Bastian, S.; Sponagel, J.; Kuryshev, V.; Sültmann, H.; Scheffner, M.; Hoppe-Seyler, K.; Hoppe-Seyler, F. Dependence of Intracellular and Exosomal microRNAs on Viral E6/E7 Oncogene Expression in HPV-positive Tumor Cells. PLoS Pathog. 2015, 11, e1004712. [Google Scholar] [CrossRef] [PubMed]
- Plazolles, N.; Humbert, J.; Vachot, L.; Verrier, B.; Hocke, C.; Halary, F. Pivotal Advance: The promotion of soluble DC-SIGN release by inflammatory signals and its enhancement of cytomegalovirus-mediated cis-infection of myeloid dendritic cells. J. Leukoc. Biol. 2011, 89, 329–342. [Google Scholar] [CrossRef]
- Morris-Love, J.; Gee, G.V.; O’Hara, B.A.; Assetta, B.; Atkinson, A.L.; Dugan, A.S.; Haley, S.A.; Atwood, W.J. JC Polyomavirus Uses Extracellular Vesicles To Infect Target Cells. mBio 2019, 10, 00379-19. [Google Scholar] [CrossRef] [Green Version]
- Handala, L.; Blanchard, E.; Raynal, P.-I.; Roingeard, P.; Morel, V.; Descamps, V.; Castelain, S.; Francois, C.; Duverlie, G.; Brochot, E.; et al. BK Polyomavirus Hijacks Extracellular Vesicles for En Bloc Transmission. J. Virol. 2020, 94, 01834-19. [Google Scholar] [CrossRef] [Green Version]
- Kim, M.H.; Lee, Y.H.; Seo, J.-W.; Moon, H.; Kim, J.S.; Kim, Y.G.; Jeong, K.-H.; Moon, J.-Y.; Lee, T.W.; Ihm, C.-G.; et al. Urinary exosomal viral microRNA as a marker of BK virus nephropathy in kidney transplant recipients. PLoS ONE 2017, 12, e0190068. [Google Scholar] [CrossRef]
- Giannecchini, S. Evidence of the Mechanism by Which Polyomaviruses Exploit the Extracellular Vesicle Delivery System during Infection. Viruses 2020, 12, 585. [Google Scholar] [CrossRef]
- Bomberger, J.; Lashua, L.; Fischer, D.; Hendricks, M. Exosome-Associated Iron Release during Respiratory Virus Co-Infection Enhances Pseudomonas aeruginosa Biofilm Growth. FASEB J. 2016, 30, 1223. [Google Scholar]
- Caruso, S.; Poon, I.K.H. Apoptotic cell-derived extracellular vesicles: More than just debris. Front. Immunol. 2018, 9, 1486. [Google Scholar] [CrossRef] [Green Version]
- Klase, Z.A.; Khakhina, S.; Schneider, A.D.B.; Callahan, M.V.; Glasspool-Malone, J.; Malone, R. Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome. PLoS Negl. Trop. Dis. 2016, 10, e0004877. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Müller, J.A.; Harms, M.; Krüger, F.; Groß, R.; Joas, S.; Hayn, M.; Dietz, A.N.; Lippold, S.; Von Einem, J.; Schubert, A.; et al. Semen inhibits Zika virus infection of cells and tissues from the anogenital region. Nat. Commun. 2018, 9, 1–14. [Google Scholar] [CrossRef]
- Zhou, W.; Woodson, M.; Sherman, M.B.; Neelakanta, G.; Sultana, H. Exosomes mediate Zika virus transmission through SMPD3 neutral Sphingomyelinase in cortical neurons. Emerg. Microbes Infect. 2019, 8, 307–326. [Google Scholar] [CrossRef]
- Sampey, G.C.; Saifuddin, M.; Schwab, A.; Barclay, R.; Punya, S.; Chung, M.-C.; Hakami, R.M.; Zadeh, M.A.; Lepene, B.; Klase, Z.A.; et al. Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA. J. Biol. Chem. 2016, 291, 1251–1266. [Google Scholar] [CrossRef] [Green Version]
- Arenaccio, C.; Anticoli, S.; Manfredi, F.; Chiozzini, C.; Olivetta, E.; Federico, M. Latent HIV-1 is activated by exosomes from cells infected with either replication-competent or defective HIV-1. Retrovirology 2015, 12, 1–17. [Google Scholar] [CrossRef] [Green Version]
- Sharp, P.M.H.; Hahn, B.H. BH: Origins of HIV and the AIDS pandemic. Cold Spring Harb. Perspect. Med. 2011, 1, a006841. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sato, K.; Aoki, J.; Misawa, N.; Daikoku, E.; Sano, K.; Tanaka, Y.; Koyanagi, Y. Modulation of Human Immunodeficiency Virus Type 1 Infectivity through Incorporation of Tetraspanin Proteins. J. Virol. 2008, 82, 1021–1033. [Google Scholar] [CrossRef] [Green Version]
- Campbell, T.D.; Khan, M.; Huang, M.-B.; Bond, V.C.; Powell, M.D. HIV-1 Nef protein is secreted into vesicles that can fuse with target cells and virions. Ethn. Dis. 2008, 18, S2. [Google Scholar]
- Yang, Y.; Han, Q.; Hou, Z.; Zhang, C.; Tian, Z.; Zhang, J. Exosomes mediate hepatitis B virus (HBV) transmission and NK-cell dysfunction. Cell. Mol. Immunol. 2017, 14, 465–475. [Google Scholar] [CrossRef]
- Jiang, B.; Himmelsbach, K.; Ren, H.; Boller, K.; Hildt, E. Subviral Hepatitis B Virus Filaments, like Infectious Viral Particles, Are Released via Multivesicular Bodies. J. Virol. 2016, 90, 3330–3341. [Google Scholar] [CrossRef] [Green Version]
- Longatti, A. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation. Viruses 2015, 7, 6707–6715. [Google Scholar] [CrossRef] [Green Version]
- Ahsan, N.A.; Sampey, G.C.; Lepene, B.; Akpamagbo, Y.; Barclay, R.A.; Iordanskiy, S.; Hakami, R.M.; Kashanchi, F. Presence of Viral RNA and Proteins in Exosomes from Cellular Clones Resistant to Rift Valley Fever Virus Infection. Front. Microbiol. 2016, 7, 139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shembade, N.; Harhaj, E.W. Role of post-translational modifications of HTLV-1 Tax in NF-κB activation. World J. Biol. Chem. 2010, 1, 13. [Google Scholar] [CrossRef] [PubMed]
- Dhib-Jalbut, S.; Hoffman, P.M.; Yamabe, T.; Sun, D.; Xia, J.; Eisenberg, H.; Bergey, G.; Ruscetti, F.W. Extracellular human T-cell lymphotropic virus type I tax protein induces cytokine production in adult human microglial cells. Ann. Neurol. 1994, 36, 787–790. [Google Scholar] [CrossRef]
- Jaworski, E.; Narayanan, A.; Van Duyne, R.; Shabbeer-Meyering, S.; Iordanskiy, S.; Saifuddin, M.; Das, R.; Afonso, P.; Sampey, G.C.; Chung, M.; et al. Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein. J. Biol. Chem. 2014, 289, 22284–22305. [Google Scholar] [CrossRef] [Green Version]
- Pfeffer, S.; Zavolan, M.; Grässer, F.A.; Chien, M.; Russo, J.J.; Ju, J.; John, B.; Enright, A.; Marks, D.; Sander, C.; et al. Identification of Virus-Encoded MicroRNAs. Science 2004, 304, 734–736. [Google Scholar] [CrossRef]
- Hoshina, S.; Sekizuka, T.; Kataoka, M.; Hasegawa, H.; Hamada, H.; Kuroda, M.; Katano, H. Profile of Exosomal and Intracellular microRNA in Gamma-Herpesvirus-Infected Lymphoma Cell Lines. PLoS ONE 2016, 11, e0162574. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chahar, H.S.; Bao, X.; Casola, A. Exosomes and Their Role in the Life Cycle and Pathogenesis of RNA Viruses. Viruses 2015, 7, 3204–3225. [Google Scholar] [CrossRef] [Green Version]
- Madison, M.N.; Okeoma, C.M. Exosomes: Implications in HIV-1 Pathogenesis. Viruses 2015, 7, 4093–4118. [Google Scholar] [CrossRef] [Green Version]
- Madison, M.N.; Jones, P.; Okeoma, C.M. Exosomes in human semen restrict HIV-1 transmission by vaginal cells and block intravaginal replication of LP-BM5 murine AIDS virus complex. Virology 2015, 482, 189–201. [Google Scholar] [CrossRef] [Green Version]
- Mori, Y.; Koike, M.; Moriishi, E.; Kawabata, A.; Tang, H.; Oyaizu, H.; Uchiyama, Y.; Yamanishi, K. Human Herpesvirus-6 Induces MVB Formation, and Virus Egress Occurs by an Exosomal Release Pathway. Traffic 2008, 9, 1728–1742. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bissig, C.; Gruenberg, J. ALIX and the multivesicular endosome: ALIX in Wonderland. Trends Cell Biol. 2014, 24, 19–25. [Google Scholar] [CrossRef] [PubMed]
- Gan, X.; Gould, S.J. Identification of an inhibitory budding signal that blocks the release of HIV particles and exosome/microvesicle proteins. Mol. Biol. Cell 2011, 22, 817–830. [Google Scholar] [CrossRef]
- Sampey, G.C.; Meyering, S.S.; Zadeh, M.A.; Saifuddin, M.; Hakami, R.M.; Kashanchi, F. Exosomes and their role in CNS viral infections. J. Neurovirol. 2014, 20, 199–208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Trajkovic, K.; Hsu, C.; Chiantia, S.; Rajendran, L.; Wenzel, D.; Wieland, F.; Schwille, P.; Brugger, B.; Simons, M. Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes. Science 2008, 319, 1244–1247. [Google Scholar] [CrossRef] [PubMed]
- Perez-Hernandez, D.; Gutiérrez-Vázquez, C.; Jorge, I.; López-Martín, S.; Ursa, A.; Sánchez-Madrid, F.; Vázquez, J.; Yáñez-Mó, M. The Intracellular Interactome of Tetraspanin-enriched Microdomains Reveals Their Function as Sorting Machineries toward Exosomes. J. Biol. Chem. 2013, 288, 11649–11661. [Google Scholar] [CrossRef] [Green Version]
- Van Niel, G.; Charrin, S.; Simoes, S.; Romao, M.; Rochin, L.; Saftig, P.; Marks, M.S.; Rubinstein, E.; Raposo, G. The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev. Cell 2011, 21, 708–721. [Google Scholar] [CrossRef] [Green Version]
- Stuffers, S.; Wegner, C.S.; Stenmark, H.; Brech, A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 2009, 10, 925–937. [Google Scholar] [CrossRef]
- Tamai, K.; Tanaka, N.; Nakano, T.; Kakazu, E.; Kondo, Y.; Inoue, J.; Shiina, M.; Fukushima, K.; Hoshino, T.; Sano, K.; et al. Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem. Biophys. Res. Commun. 2010, 399, 384–390. [Google Scholar] [CrossRef]
- Schwartz, S.L.; Cao, C.; Pylypenko, O.; Rak, A.; Wandinger-Ness, A. Rab GTPases at a glance. J. Cell Sci. 2007, 120, 3905–3910. [Google Scholar] [CrossRef] [Green Version]
- Baietti, M.F.; Zhang, Z.; Mortier, E.; Melchior, A.; Degeest, G.; Geeraerts, A.; Ivarsson, Y.; Depoortere, F.; Coomans, C.; Vermeiren, E.; et al. Syndecan–syntenin–ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 2012, 14, 677–685. [Google Scholar] [CrossRef] [PubMed]
- Colombo, M.; Raposo, G.; Théry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014, 30, 255–289. [Google Scholar] [CrossRef] [PubMed]
- Fader, C.M.; Sánchez, D.G.; Mestre, M.B.; Colombo, M.I. TI-VAMP/VAMP7 and VAMP3/cellubrevin: Two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim. Biophys. Acta BBA Mol. Cell Res. 2009, 1793, 1901–1916. [Google Scholar] [CrossRef] [Green Version]
- Savina, A.; Fader, C.M.; Damiani, M.T.; Colombo, M.I. Rab11 Promotes Docking and Fusion of Multivesicular Bodies in a Calcium-Dependent Manner. Traffic 2005, 6, 131–143. [Google Scholar] [CrossRef]
- Livshits, M.A.; Khomyakova, E.; Evtushenko, E.; Lazarev, V.N.; Kulemin, N.; Semina, S.E.; Generozov, E.; Govorun, V.M. Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol. Sci. Rep. 2015, 5, 1–14. [Google Scholar] [CrossRef]
- Johnstone, R.M. Maturation of reticulocytes: Formation of exosomes as a mechanism for shedding membrane proteins. Biochem. Cell Biol. 1992, 70, 179–190. [Google Scholar] [CrossRef]
- Théry, C.; Amigorena, S.; Raposo, G.; Clayton, A. Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids. Curr. Protoc. Cell Biol. 2006, 30, 3–22. [Google Scholar] [CrossRef]
- Cvjetkovic, A.; Lötvall, J.; Lässer, C. The influence of rotor type and centrifugation time on the yield and purity of extracellular vesicles. J. Extracell. Vesicles 2014, 3, 23111. [Google Scholar] [CrossRef]
- Böing, A.N.; van der Pol, E.; Grootemaat, A.E.; Coumans, F.A.W.; Sturk, A.; Nieuwland, R. Single-step isolation of extracellular vesicles by size-exclusion chromatography. J. Extracell. Vesicles 2014, 3, 23430. [Google Scholar] [CrossRef]
- Cantin, R.; Diou, J.; Bélanger, D.; Tremblay, A.M.; Gilbert, C. Discrimination between exosomes and HIV-1: Purification of both vesicles from cell-free supernatants. J. Immunol. Methods 2008, 338, 21–30. [Google Scholar] [CrossRef] [PubMed]
- Ford, T.; Graham, J.; Rickwood, D. Iodixanol: A Nonionic Iso-osmotic Centrifugation Medium for the Formation of Self-Generated Gradients. Anal. Biochem. 1994, 220, 360–366. [Google Scholar] [CrossRef]
- Rider, M.A.; Hurwitz, S.N.; Meckes, D.G., Jr. ExtraPEG: A Polyethylene Glycol-Based Method for Enrichment of Extracellular Vesicles. Sci. Rep. 2016, 6, 23978. [Google Scholar] [CrossRef] [PubMed]
- Vergauwen, G.; Dhondt, B.; Van Deun, J.; De Smedt, E.; Berx, G.; Timmerman, E.; Gevaert, K.; Miinalainen, I.; Cocquyt, V.; Braems, G.; et al. Confounding factors of ultrafiltration and protein analysis in extracellular vesicle research. Sci. Rep. 2017, 7, 1–12. [Google Scholar] [CrossRef] [Green Version]
- Fitzgerald, J.; Leonard, P.; Darcy, E.; Sharma, S.; O’Kennedy, R. Immunoaffinity Chromatography: Concepts and Applications. Protein Chromatogr. 2017, 1485, 27–51. [Google Scholar] [CrossRef]
- Li, P.; Kaslan, M.; Lee, S.H.; Yao, J.; Gao, Z. Progress in Exosome Isolation Techniques. Theranostics 2017, 7, 789–804. [Google Scholar] [CrossRef]
- Zarovni, N.; Corrado, A.; Guazzi, P.; Zocco, D.; Lari, E.; Radano, G.; Muhhina, J.; Fondelli, C.; Gavrilova, J.; Chiesi, A. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods 2015, 87, 46–58. [Google Scholar] [CrossRef]
- Wu, Y.; Deng, W.; Klinke, D.J., II. Exosomes: Improved methods to characterize their morphology, RNA content, and surface protein biomarkers. Analyst 2015, 140, 6631–6642. [Google Scholar] [CrossRef] [Green Version]
- Maas, S.L.N.; Broekman, M.; Nolte, M.L.D.; Hoen, T.; Mastrobattista, E.; Schiffelers, R.M.; Wauben, M.H.M.; Broekman, M.L.D.; Hoen, E.N.M. Possibilities and limitations of current technologies for quantification of biological extracellular vesicles and synthetic mimics. J. Control. Release 2015, 200, 87–96. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murray, C.J.L.; Ortblad, K.F.; Guinovart, C.; Lim, S.S.; Wolock, T.M.; Roberts, D.A.; Dansereau, E.A.; Graetz, N.; Barber, R.M.; Brown, J.C.; et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014, 384, 1005–1070. [Google Scholar] [CrossRef] [Green Version]
- Zhang, W.; Jiang, X.; Bao, J.; Wang, Y.; Liu, H.; Tang, L. Exosomes in Pathogen Infections: A Bridge to Deliver Molecules and Link Functions. Front. Immunol. 2018, 9, 90. [Google Scholar] [CrossRef] [Green Version]
- Izquierdo-Useros, N.; Puertas, M.C.; Borras, F.E.; Blanco, J.; Martinez-Picado, J. Exosomes and retroviruses: The chicken or the egg? Cell. Microbiol. 2011, 13, 10–17. [Google Scholar] [CrossRef]
- Ott, D.E. Cellular proteins detected in HIV-1. Rev. Med Virol. 2008, 18, 159–175. [Google Scholar] [CrossRef]
- Wubbolts, R.; Leckie, R.S.; Veenhuizen, P.T.M.; Schwarzmann, G.; Möbius, W.; Hoernschemeyer, J.; Slot, J.-S.; Geuze, H.J.; Stoorvogel, W. Proteomic and biochemical analyses of human B cell-derived exosomes Potential implications for their function and multivesicular body formation. J. Biol. Chem. 2003, 278, 10963–10972. [Google Scholar] [CrossRef] [Green Version]
- Krishnamoorthy, L.; Bess, J.W.; Preston, A.B.; Nagashima, K.; Mahal, L.K. HIV-1 and microvesicles from T cells share a common glycome, arguing for a common origin. Nat. Chem. Biol. 2009, 5, 244–250. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grigorov, B.; Attuil-Audenis, V.; Perugi, F.; Nedelec, M.; Watson, S.; Pique, C.; Darlix, J.-L.; Conjeaud, H.; Muriaux, D. A role for CD81 on the late steps of HIV-1 replication in a chronically infected T cell line. Retrovirology 2009, 6, 28. [Google Scholar] [CrossRef] [Green Version]
- Savina, A.; Vidal, M.; Colombo, M.I. The exosome pathway in K562 cells is regulated by Rab11. J. Cell Sci. 2002, 115, 2505–2515. [Google Scholar] [CrossRef]
- Bruce, E.A.; Digard, P.; Stuart, A.D. The Rab11 Pathway Is Required for Influenza A Virus Budding and Filament Formation. J. Virol. 2010, 84, 5848–5859. [Google Scholar] [CrossRef] [Green Version]
- Rowe, R.; Suszko, J.W.; Pekosz, A. Roles for the recycling endosome, Rab8, and Rab11 in hantavirus release from epithelial cells. Virology 2008, 382, 239–249. [Google Scholar] [CrossRef] [Green Version]
- Utley, T.J.; Ducharme, N.; Varthakavi, V.; Shepherd, B.E.; Santangelo, P.J.; Lindquist, M.E.; Goldenring, J.R.; Crowe, J.E. Respiratory syncytial virus uses a Vps4-independent budding mechanism controlled by Rab11-FIP2. Proc. Natl. Acad. Sci. USA 2008, 105, 10209–10214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abrami, L.; Brandi, L.; Moayeri, M.; Brown, M.J.; Krantz, B.A.; Leppla, S.H.; Van Der Goot, F.G. Hijacking Multivesicular Bodies Enables Long-Term and Exosome-Mediated Long-Distance Action of Anthrax Toxin. Cell Rep. 2013, 5, 986–996. [Google Scholar] [CrossRef] [Green Version]
- Bhuin, T.; Roy, J.K. Rab11 in Disease Progression. Int. J. Mol. Cell. Med. 2015, 4, 1–8. [Google Scholar]
- Ostrowski, M.; Carmo, N.B.; Krumeich, S.; Fanget, I.; Raposo, G.; Savina, A.; Moita, C.F.; Schauer, K.; Hume, A.N.; Freitas, R.P.; et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 2010, 12, 19–30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bobrie, A.; Krumeich, S.; Reyal, F.; Recchi, C.; Moita, L.; Seabra, M.; Ostrowski, M.; Théry, C. Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression. Cancer Res. 2012, 72, 4920–4930. [Google Scholar] [CrossRef] [Green Version]
- Fraile-Ramos, A.; Cepeda, V.; Elstak, E.; Van Der Sluijs, P. Rab27a Is Required for Human Cytomegalovirus Assembly. PLoS ONE 2010, 5, e15318. [Google Scholar] [CrossRef]
- Gerber, P.P.; Cabrini, M.; Jancic, C.; Paoletti, L.; Banchio, C.; Von Bilderling, C.; Sigaut, L.; Pietrasanta, L.; Duette, G.; Freed, E.O.; et al. Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate. J. Cell Biol. 2015, 209, 435–452. [Google Scholar] [CrossRef] [Green Version]
- Meng, B.; Ip, N.C.Y.; Prestwood, L.J.; Abbink, T.E.M.; Lever, A.M.L. Evidence that the endosomal sorting complex required for transport-II (ESCRT-II) is required for efficient human immunodeficiency virus-1 (HIV-1) production. Retrovirology 2015, 12, 1–15. [Google Scholar] [CrossRef] [Green Version]
- Miranda-Saksena, M.; Boadle, R.A.; Aggarwal, A.; Tijono, B.; Rixon, F.J.; Diefenbach, R.J.; Cunningham, A.L. Herpes Simplex Virus Utilizes the Large Secretory Vesicle Pathway for Anterograde Transport of Tegument and Envelope Proteins and for Viral Exocytosis from Growth Cones of Human Fetal Axons. J. Virol. 2009, 83, 3187–3199. [Google Scholar] [CrossRef] [Green Version]
- Bello-Morales, R.; Crespillo, A.J.; Fraile-Ramos, A.; Tabarés, E.; Alcina, A.; López-Guerrero, J.A. Role of the small GTPase Rab27a during Herpes simplex virus infection of oligodendrocytic cells. BMC Microbiol. 2012, 12, 265. [Google Scholar] [CrossRef] [Green Version]
- White, I.J.; Bailey, L.M.; Aghakhani, M.R.; Moss, S.E.; Futter, C.E. EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation. EMBO J. 2006, 25, 1–12. [Google Scholar] [CrossRef] [Green Version]
- Morales-Sánchez, A.; Fuentes-Pananá, E.M. Human Viruses and Cancer. Viruses 2014, 6, 4047–4079. [Google Scholar] [CrossRef] [Green Version]
- Chugh, P.E.; Sin, S.-H.; Ozgur, S.; Henry, D.H.; Menezes, P.; Griffith, J.; Eron, J.J.; Damania, B.; Dittmer, D.P. Systemically Circulating Viral and Tumor-Derived MicroRNAs in KSHV-Associated Malignancies. PLoS Pathog. 2013, 9, e1003484. [Google Scholar] [CrossRef] [Green Version]
- Canitano, A.; Venturi, G.; Borghi, M.; Ammendolia, M.G.; Fais, S. Exosomes released in vitro from Epstein–Barr virus (EBV)-infected cells contain EBV-encoded latent phase mRNAs. Cancer Lett. 2013, 337, 193–199. [Google Scholar] [CrossRef]
- Meckes, D.G.; Gunawardena, H.P.; Dekroon, R.M.; Heaton, P.R.; Edwards, R.H.; Ozgur, S.; Griffith, J.D.; Damania, B.; Raab-Traub, N. Modulation of B-cell exosome proteins by gamma herpesvirus infection. Proc. Natl. Acad. Sci. USA 2013, 110, E2925–E2933. [Google Scholar] [CrossRef] [Green Version]
- Edwards, R.H.; Marquitz, A.R.; Raab-Traub, N. Epstein-Barr Virus BART MicroRNAs Are Produced from a Large Intron prior to Splicing. J. Virol. 2008, 82, 9094–9106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hooykaas, M.J.G.; Kruse, E.; Wiertz, E.J.H.J.; Lebbink, R.J. Comprehensive profiling of functional Epstein-Barr virus miRNA expression in human cell lines. BMC Genom. 2016, 17, 1–13. [Google Scholar] [CrossRef] [Green Version]
- Shinozaki-Ushiku, A.; Kunita, A.; Isogai, M.; Hibiya, T.; Ushiku, T.; Takada, K.; Fukayama, M. Profiling of Virus-Encoded MicroRNAs in Epstein-Barr Virus-Associated Gastric Carcinoma and Their Roles in Gastric Carcinogenesis. J. Virol. 2015, 89, 5581–5591. [Google Scholar] [CrossRef] [Green Version]
- Gallo, A.; Vella, S.; Miele, M.; Timoneri, F.; Di Bella, M.; Bosi, S.; Sciveres, M.; Conaldi, P.G. Global profiling of viral and cellular non-coding RNAs in Epstein–Barr virus-induced lymphoblastoid cell lines and released exosome cargos. Cancer Lett. 2017, 388, 334–343. [Google Scholar] [CrossRef]
- Verweij, F.; Van Eijndhoven, M.A.J.; Hopmans, E.S.; Vendrig, T.; Wurdinger, T.; Cahir-McFarland, E.; Kieff, E.; Geerts, D.; van der Kant, R.; Neefjes, J.; et al. LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation. EMBO J. 2011, 30, 2115–2129. [Google Scholar] [CrossRef] [PubMed]
- Iwakiri, D.; Zhou, L.; Samanta, M.; Matsumoto, M.; Ebihara, T.; Seya, T.; Imai, S.; Fujieda, M.; Kawa, K.; Takada, K. Epstein-Barr virus (EBV)–encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3. J. Exp. Med. 2009, 206, 2091–2099. [Google Scholar] [CrossRef] [Green Version]
- Wu, L.; KewalRamani, V.N. Dendritic-cell interactions with HIV: Infection and viral dissemination. Nat. Rev. Immunol. 2006, 6, 859–868. [Google Scholar] [CrossRef] [PubMed]
- Fang, Y.; Wu, N.; Gan, X.; Yan, W.; Morrell, J.C.; Gould, S.J. Higher-Order Oligomerization Targets Plasma Membrane Proteins and HIV Gag to Exosomes. PLoS Biol. 2007, 5, e158. [Google Scholar] [CrossRef] [Green Version]
- Lenassi, M.; Cagney, G.; Liao, M.; Vaupotič, T.; Bartholomeeusen, K.; Cheng, Y.; Krogan, N.J.; Plemenitaš, A.; Peterlin, B. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic 2010, 11, 110–122. [Google Scholar] [CrossRef] [Green Version]
- De Carvalho, J.V.; de Castro, R.O.; da Silva, E.Z.; Silveira, P.P.; da Silva-Januário, M.E.; Arruda, E.; Jamur, M.C.; Oliver, C.; Aguiar, R.S.; DaSilva, L.L. Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection. PLoS ONE 2014, 9, e113691. [Google Scholar] [CrossRef] [Green Version]
- Bernard, M.; Zhao, H.; Yue, S.C.; Anandaiah, A.; Koziel, H.; Tachado, S.D. Novel HIV-1 MiRNAs Stimulate TNFα Release in Human Macrophages via TLR8 Signaling Pathway. PLoS ONE 2014, 9, e106006. [Google Scholar] [CrossRef]
- Narayanan, A.; Iordanskiy, S.; Das, R.; Van Duyne, R.; Santos, S.; Jaworski, E.; Guendel, I.; Sampey, G.; Dalby, E.; Iglesias-Ussel, M.; et al. Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA. J. Biol. Chem. 2013, 288, 20014–20033. [Google Scholar] [CrossRef] [Green Version]
- Arenaccio, C.; Chiozzini, C.; Columba-Cabezas, S.; Manfredi, F.; Federico, M. Cell activation and HIV-1 replication in unstimulated CD4+ T lymphocytes ingesting exosomes from cells expressing defective HIV-1. Retrovirology 2014, 11, 1–16. [Google Scholar] [CrossRef] [Green Version]
- Arenaccio, C.; Chiozzini, C.; Columba-Cabezas, S.; Manfredi, F.; Affabris, E.; Baur, A.; Federico, M. 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. 2014, 88, 11529–11539. [Google Scholar] [CrossRef] [Green Version]
- Izquierdo-Useros, N.; Naranjo-Gomez, M.; Archer, J.; Hatch, S.C.; Erkizia, I.; Blanco, J.; Borras, F.E.; Puertas, M.C.; Connor, J.; Fernández-Figueras, M.T.; et al. Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway. Blood J. Am. Soc. Hematol. 2009, 113, 2732–2741. [Google Scholar] [CrossRef] [Green Version]
- Jolly, C.; Sattentau, Q.J. Human Immunodeficiency Virus Type 1 Assembly, Budding, and Cell-Cell Spread in T Cells Take Place in Tetraspanin-Enriched Plasma Membrane Domains. J. Virol. 2007, 81, 7873–7884. [Google Scholar] [CrossRef] [Green Version]
- Mack, M.; Kleinschmidt, A.; Brühl, H.; Klier, C.; Nelson, P.J.; Cihak, J.; Plachý, J.; Stangassinger, M.; Erfle, V.; Schlöndorff, D. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection. Nat. Med. 2000, 6, 769–775. [Google Scholar] [CrossRef]
- Rozmyslowicz, T.; Majka, M.; Kijowski, J.; Murphy, S.L.; Conover, D.O.; Poncz, M.; Ratajczak, J.; Gaulton, G.N.; Ratajczak, M.Z. Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS 2003, 17, 33–42. [Google Scholar] [CrossRef]
- Narayanan, A.; Jaworski, E.; Van Duyne, R.; Iordanskiy, S.; Guendel, I.; Das, R.; Currer, R.; Sampey, G.; Chung, M.; Kehn-Hall, K.; et al. Exosomes derived from HTLV-1 infected cells contain the viral protein Tax. Retrovirology 2014, 11, O46. [Google Scholar] [CrossRef] [Green Version]
- Anderson, M.; Lepene, B.; Kashanchi, F.; Jacobson, S. Detection of Human T-Cell Lymphotropic Virus Type I Proteins in Exosomes from HAM/TSP Patient CSF by Novel Nanotrap Technology (S12. 007); AAN Enterprises: Faridabad, India, 2015. [Google Scholar]
- Chivero, E.T.; Bhattarai, N.; Rydze, R.T.; Winters, M.A.; Holodniy, M.; Stapleton, J.T. Human pegivirus RNA is found in multiple blood mononuclear cells in vivo and serum-derived viral RNA-containing particles are infectious in vitro. J. Gen. Virol. 2014, 95, 1307. [Google Scholar] [CrossRef] [PubMed]
- Fleming, A.; Sampey, G.; Chung, M.-C.; Bailey, C.; Van Hoek, M.; Kashanchi, F.; Hakami, R.M. The carrying pigeons of the cell: Exosomes and their role in infectious diseases caused by human pathogens. Pathog. Dis. 2014, 71, 109–120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nanbo, A.; Kawanishi, E.; Yoshida, R.; Yoshiyama, H. Exosomes Derived from Epstein-Barr Virus-Infected Cells Are Internalized via Caveola-Dependent Endocytosis and Promote Phenotypic Modulation in Target Cells. J. Virol. 2013, 87, 10334–10347. [Google Scholar] [CrossRef] [Green Version]
- Keryer-Bibens, C.; Pioche-Durieu, C.; Villemant, C.; Souquère, S.; Nishi, N.; Hirashima, M.; Middeldorp, J.; Busson, P. Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9. BMC Cancer 2006, 6, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Klinker, M.W.; Lizzio, V.; Reed, T.J.; Fox, D.A.; Lundy, S.K. Human B cell-derived lymphoblastoid cell lines constitutively produce Fas ligand and secrete MHCII+ FasL+ killer exosomes. Front. Immunol. 2014, 5, 144. [Google Scholar] [CrossRef] [Green Version]
- Klibi, J.; Niki, T.; Adhikary, D.; Mautner, J.; Busson, P.; Riedel, A.; Pioche-Durieu, C.; Souquere, S.; Rubinstein, E.; Le Moulec, S.; et al. Blood diffusion and Th1-suppressive effects of galectin-9–containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells. Blood J. Am. Soc. Hematol. 2009, 113, 1957–1966. [Google Scholar] [CrossRef] [Green Version]
- Wang, D.; Liebowitz, D.; Kieff, E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 1985, 43, 831–840. [Google Scholar] [CrossRef]
- Mosialos, G.; Birkenbacht, M.; Yalamanchill, R.; Van Arsdale, T.; Ware, C.; Kleff, E. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell 1995, 80, 389–399. [Google Scholar] [CrossRef] [Green Version]
- Lavorgna, A.; Harhaj, E.W. EBV LMP1: New and shared pathways to NF-κB activation. Proc. Natl. Acad. Sci. USA 2012, 109, 2188–2189. [Google Scholar] [CrossRef] [Green Version]
- Longnecker, R.; Kieff, E. A second Epstein-Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1. J. Virol. 1990, 64, 2319–2326. [Google Scholar] [CrossRef] [Green Version]
- Caldwell, R.G.; Wilson, J.B.; Anderson, S.J.; Longnecker, R. Epstein-Barr Virus LMP2A Drives B Cell Development and Survival in the Absence of Normal B Cell Receptor Signals. Immunity 1998, 9, 405–411. [Google Scholar] [CrossRef] [Green Version]
- Casola, S.; Otipoby, K.L.; Alimzhanov, M.; Humme, S.; Uyttersprot, N.; Kutok, J.L.; Carroll, M.C.; Rajewsky, K. B cell receptor signal strength determines B cell fate. Nat. Immunol. 2004, 5, 317–327. [Google Scholar] [CrossRef]
- Oldstone, M.B. Viral persistence: Parameters, mechanisms and future predictions. Virology 2006, 344, 111–118. [Google Scholar] [CrossRef] [PubMed]
- Cox, J.E.; Sullivan, C.S. Balance and Stealth: The Role of Noncoding RNAs in the Regulation of Virus Gene Expression. Annu. Rev. Virol. 2014, 1, 89–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nicoll, M.; Proença, J.; Efstathiou, S. The molecular basis of herpes simplex virus latency. FEMS Microbiol. Rev. 2012, 36, 684–705. [Google Scholar] [CrossRef]
- Umbach, J.L.; Kramer, M.F.; Jurak, I.; Karnowski, H.W.; Coen, D.M.; Cullen, B.R. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 2008, 454, 780–783. [Google Scholar] [CrossRef] [Green Version]
- Du, T.; Han, Z.; Zhou, G.; Roizman, B. Patterns of accumulation of miRNAs encoded by herpes simplex virus during productive infection, latency, and on reactivation. Proc. Natl. Acad. Sci. USA 2015, 112, E49–E55. [Google Scholar] [CrossRef] [Green Version]
- Piedade, D.; Azevedo-Pereira, J.M. The Role of microRNAs in the Pathogenesis of Herpesvirus Infection. Viruses 2016, 8, 156. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Han, Z.; Liu, X.; Chen, X.; Zhou, X.; Du, T.; Roizman, B.; Zhou, G. miR-H28 and miR-H29 expressed late in productive infection are exported and restrict HSV-1 replication and spread in recipient cells. Proc. Natl. Acad. Sci. USA 2016, 113, E894–E901. [Google Scholar] [CrossRef] [Green Version]
- Mclauchlan, J.; Addison, C.; Craigie, M.C.; Rixon, F.J. Noninfectious L-particles supply functions which can facilitate infection by HSV-1. Virology 1992, 190, 682–688. [Google Scholar] [CrossRef]
- Rixon, F.J.; Addison, C.; Mclauchlan, J. Assembly of enveloped tegument structures (L particles) can occur independently of virion maturation in herpes simplex virus type 1-infected cells. J. Gen. Virol. 1992, 73, 277–284. [Google Scholar] [CrossRef]
- Heilingloh, C.S.; Kummer, M.; Mühl-Zürbes, P.; Drassner, C.; Daniel, C.; Klewer, M.; Steinkasserer, A. L Particles Transmit Viral Proteins from Herpes Simplex Virus 1-Infected Mature Dendritic Cells to Uninfected Bystander Cells, Inducing CD83 Downmodulation. J. Virol. 2015, 89, 11046–11055. [Google Scholar] [CrossRef] [Green Version]
- Chen, R.; Zhao, X.; Wang, Y.; Xie, Y.; Liu, J. Hepatitis B virus X protein is capable of down-regulating protein level of host antiviral protein APOBEC3G. Sci. Rep. 2017, 7, 1–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chai, N.; Chang, H.E.; Nicolas, E.; Han, Z.; Jarnik, M.; Taylor, J. Properties of Subviral Particles of Hepatitis B Virus. J. Virol. 2008, 82, 7812–7817. [Google Scholar] [CrossRef] [Green Version]
- Kadiu, I.; Narayanasamy, P.; Dash, P.K.; Zhang, W.; Gendelman, H.E. Biochemical and Biologic Characterization of Exosomes and Microvesicles as Facilitators of HIV-1 Infection in Macrophages. J. Immunol. 2012, 189, 744–754. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Konadu, K.A.; Chu, J.; Huang, M.B.; Amancha, P.K.; Armstrong, W.S.; Powell, M.D.; Villinger, F.; Bond, V.C. Association of Cytokines with Exosomes in the Plasma of HIV-1–Seropositive Individuals. J. Infect. Dis. 2015, 211, 1712–1716. [Google Scholar] [CrossRef]
- Esser, M.T.; Graham, D.R.; Coren, L.V.; Trubey, C.M.; Bess, J.W.; Arthur, L.O.; Ott, D.E.; Lifson, J.D. Differential Incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and Major Histocompatibility Complex Class I and II Molecules into Human Immunodeficiency Virus Type 1 Virions and Microvesicles: Implications for Viral Pathogenesis and Immune Regulation. J. Virol. 2001, 75, 6173–6182. [Google Scholar] [CrossRef] [Green Version]
- Tumne, A.; Prasad, V.S.; Chen, Y.; Stolz, D.B.; Saha, K.; Ratner, D.M.; Ding, M.; Watkins, S.C.; Gupta, P. Noncytotoxic suppression of human immunodeficiency virus type 1 transcription by exosomes secreted from CD8+ T cells. J. Virol. 2009, 83, 4354–4364. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khatua, A.K.; Taylor, H.E.; Hildreth, J.E.K.; Popik, W. Exosomes Packaging APOBEC3G Confer Human Immunodeficiency Virus Resistance to Recipient Cells. J. Virol. 2009, 83, 512–521. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Z.; Zhang, X.; Yu, Q.; He, J.J. Exosome-associated hepatitis C virus in cell cultures and patient plasma. Biochem. Biophys. Res. Commun. 2014, 455, 218–222. [Google Scholar] [CrossRef] [PubMed]
- Badierah, R.A.; Uversky, V.N.; Redwan, E.M. Dancing with Trojan horses: An interplay between the extracellular vesicles and viruses. J. Biomol. Struct. Dyn. 2020, 39, 1–27. [Google Scholar] [CrossRef]
- Elrashdy, F.; Aljaddawi, A.A.; Redwan, E.M.; Uversky, V.N. On the potential role of exosomes in the COVID-19 reinfection/reactivation opportunity. J. Biomol. Struct. Dyn. 2021, 39, 5831–5842. [Google Scholar] [CrossRef]
- Zhang, C.; Shi, L.; Wang, F.-S. Liver injury in COVID-19: Management and challenges. Lancet Gastroenterol. Hepatol. 2020, 5, 428–430. [Google Scholar] [CrossRef]
- Zhang, X.-J.; Qin, J.-J.; Cheng, X.; Shen, L.; Zhao, Y.-C.; Yuan, Y.; Lei, F.; Chen, M.-M.; Yang, H.; Bai, L.; et al. In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab. 2020, 32, 176–187. [Google Scholar] [CrossRef]
- Song, J.-W.; Lam, S.M.; Fan, X.; Cao, W.-J.; Wang, S.-Y.; Tian, H.; Chua, G.H.; Zhang, C.; Meng, F.-P.; Xu, Z.; et al. Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis. Cell Metab. 2020, 32, 188–202. [Google Scholar] [CrossRef]
- Song, Y.; Liu, P.; Shi, X.L.; Chu, Y.L.; Zhang, J.; Xia, J.; Gao, X.Z.; Qu, T.; Wang, M.Y. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut 2020, 69, 1143–1144. [Google Scholar] [CrossRef] [Green Version]
- Kwon, Y.; Nukala, S.B.; Srivastava, S.; Miyamoto, H.; Ismail, N.I.; Ong, S.-B.; Lee, W.H.; Ong, S. Detection of Viral RNA Fragments in Human iPSC-Cardiomyocytes following Treatment with Extracellular Vesicles from SARS-CoV-2 Coding-Sequence-Overexpressing Lung Epithelial Cells. bioRxiv 2020. [Google Scholar] [CrossRef]
- Bouhaddou, M.; Memon, D.; Meyer, B.; White, K.M.; Rezelj, V.V.; Marrero, M.C.; Polacco, B.J.; Melnyk, J.E.; Ulferts, S.; Kaake, R.M.; et al. The global phosphorylation landscape of SARS-CoV-2 infection. Cell 2020, 182, 685–712. [Google Scholar] [CrossRef]
- Qian, Z.; Travanty, E.A.; Oko, L.; Edeen, K.; Berglund, A.; Wang, J.; Ito, Y.; Holmes, K.V.; Mason, R.J. Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus. Am. J. Respir. Cell Mol. Biol. 2013, 48, 742–748. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Uversky, V.N.; Elrashdy, F.; Aljadawi, A.; Ali, S.M.; Khan, R.H.; Redwan, E.M. Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How? J. Neurosci. Res. 2020, 99, 750–777. [Google Scholar] [CrossRef]
- Su, H.; Yang, M.; Wan, C.; Yi, L.-X.; Tang, F.; Zhu, H.-Y.; Yi, F.; Yang, H.-C.; Fogo, A.B.; Nie, X.; et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020, 98, 219–227. [Google Scholar] [CrossRef]
- Farkash, E.A.; Wilson, A.M.; Jentzen, J.M. Ultrastructural evidence for direct renal infection with SARS-CoV-2. J. Am. Soc. Nephrol. 2020, 31, 1683–1687. [Google Scholar] [CrossRef]
- Ling, Y.; Xu, S.-B.; Lin, Y.-X.; Tian, D.; Zhu, Z.-Q.; Dai, F.-H.; Wu, F.; Song, Z.-G.; Huang, W.; Chen, J.; et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin. Med. J. 2020, 133, 1039–1043. [Google Scholar] [CrossRef] [PubMed]
- Wang, W.; Xu, Y.; Gao, R.; Lu, R.; Han, K.; Wu, G.; Tan, W. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020, 323, 1843–1844. [Google Scholar] [CrossRef] [Green Version]
- Mason, R.J. Pathogenesis of COVID-19 from a cell biology perspective. Eur. Respir. J. 2020, 55, 2000607. [Google Scholar] [CrossRef] [Green Version]
- Mönkemüller, K.; Fry, L.; Rickes, S. COVID-19, coronavirus, SARS-CoV-2 and the small bowel. Rev. Esp. Enferm. Dig. 2020, 112, 383–388. [Google Scholar]
- Monteil, V.; Kwon, H.; Prado, P.; Hagelkrüys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; del Pozo, C.H.; Prosper, F.; et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020, 181, 905–913.e7. [Google Scholar] [CrossRef] [PubMed]
- Varga, Z.; Flammer, A.J.; Steiger, P.; Haberecker, M.; Andermatt, R.; Zinkernagel, A.S.; Mehra, M.R.; Schuepbach, R.A.; Ruschitzka, F.; Moch, H. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020, 395, 10234. [Google Scholar] [CrossRef]
- Knoops, K.; Kikkert, M.; Worm, S.H.E.V.D.; Zevenhoven-Dobbe, J.C.; Van Der Meer, Y.; Koster, A.J.; Mommaas, A.M.; Snijder, E.J. SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum. PLoS Biol. 2008, 6, e226. [Google Scholar] [CrossRef]
- Knoops, K.; Barcena, M.; Limpens, R.; Koster, A.; Mommaas, A.M.; Snijder, E.J. Ultrastructural Characterization of Arterivirus Replication Structures: Reshaping the Endoplasmic Reticulum To Accommodate Viral RNA Synthesis. J. Virol. 2012, 86, 2474–2487. [Google Scholar] [CrossRef] [Green Version]
- El-Fakharany, E.M.; El-Maradny, Y.; Othman, A.; Gerges, M.; Belal, F.; Behery, E. COVID-19 coronavirus: Pathogenesis, clinical features, diagnostics, epidemiology, prevention and control. Microb. Biosyst. 2020, 5, 1–14. [Google Scholar] [CrossRef]
- Al-Mulla, H.M.N.; Turrell, L.; Smith, N.M.; Payne, L.; Baliji, S.; Züst, R.; Thiel, V.; Baker, S.C.; Siddell, S.; Neuman, B.W. Competitive Fitness in Coronaviruses Is Not Correlated with Size or Number of Double-Membrane Vesicles under Reduced-Temperature Growth Conditions. mBio 2014, 5, e01017-14. [Google Scholar] [CrossRef] [Green Version]
- Angelini, M.M.; Akhlaghpour, M.; Neuman, B.W.; Buchmeier, M.J. Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles. mBio 2013, 4, e00524-13. [Google Scholar] [CrossRef] [Green Version]
- Oudshoorn, D.; Rijs, K.; Limpens, R.; Groen, K.; Koster, A.J.; Snijder, E.J.; Kikkert, M.; Bárcena, M. Expression and Cleavage of Middle East Respiratory Syndrome Coronavirus nsp3-4 Polyprotein Induce the Formation of Double-Membrane Vesicles That Mimic Those Associated with Coronaviral RNA Replication. mBio 2017, 8, e01658-17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, J.; Liu, K.; Liu, Y.; Xu, Y.; Zhang, F.; Yang, H.; Liu, J.; Pan, T.; Chen, J.; Wu, M.; et al. Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity. Nat. Immunol. 2013, 14, 793–803. [Google Scholar] [CrossRef]
- Koppers-Lalic, D.; Hogenboom, M.M.; Middeldorp, J.; Pegtel, D.M. Virus-modified exosomes for targeted RNA delivery; A new approach in nanomedicine. Adv. Drug Deliv. Rev. 2013, 65, 348–356. [Google Scholar] [CrossRef] [PubMed]
- Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J.A. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29, 341–345. [Google Scholar] [CrossRef]
- Viaud, S.; Théry, C.; Ploix, S.; Tursz, T.; Lapierre, V.; Lantz, O.; Zitvogel, L.; Chaput, N. Dendritic Cell-Derived Exosomes for Cancer Immunotherapy: What’s Next? Cancer Res. 2010, 70, 1281–1285. [Google Scholar] [CrossRef] [Green Version]
- Aline, F.; Bout, D.; Amigorena, S.; Roingeard, P.; Dimier-Poisson, I. Toxoplasma gondii Antigen-Pulsed-Dendritic Cell-Derived Exosomes Induce a Protective Immune Response against T. gondii Infection. Infect. Immun. 2004, 72, 4127–4137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van den Boorn, J.G.; Schlee, M.; Coch, C.; Hartmann, G. SiRNA delivery with exosome nanoparticles. Nat. Biotechnol. 2011, 29, 325–326. [Google Scholar] [CrossRef] [PubMed]
- Jesus, S.; Soares, E.; Cruz, M.T.; Borges, O. Exosomes as adjuvants for the recombinant hepatitis B antigen: First report. Eur. J. Pharm. Biopharm. 2018, 133, 1–11. [Google Scholar] [CrossRef]
- Ferrantelli, F.; Manfredi, F.; Chiozzini, C.; Anticoli, S.; Olivetta, E.; Arenaccio, C.; Federico, M. DNA Vectors Generating Engineered Exosomes Potential CTL Vaccine Candidates Against AIDS, Hepatitis B, and Tumors. Mol. Biotechnol. 2018, 60, 773–782. [Google Scholar] [CrossRef]
- Näslund, T.I.; Paquin-Proulx, D.; Paredes, P.T.; Vallhov, H.; Sandberg, J.K.; Gabrielsson, S. Exosomes from breast milk inhibit HIV-1 infection of dendritic cells and subsequent viral transfer to CD4+ T cells. AIDS 2014, 28, 171–180. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Orleans, L.A.; Vice, H.; Manchikanti, L. Expanded umbilical cord mesenchymal stem cells (UC-MSCs) as a therapeutic strategy in managing critically ill COVID-19 patients: The case for compassionate use. Pain Physician 2020, 23, E71–E83. [Google Scholar]
- Tsiapalis, D.; O’Driscoll, L. Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications. Cells 2020, 9, 991. [Google Scholar] [CrossRef] [Green Version]
- Bari, E.; Ferrarotti, I.; Torre, M.L.; Corsico, A.G.; Perteghella, S. Mesenchymal stem/stromal cell secretome for lung regeneration: The long way through “pharmaceuticalization” for the best formulation. J. Control. Release 2019, 309, 11–24. [Google Scholar] [CrossRef] [PubMed]
- Bari, E.; Ferrarotti, I.; Saracino, L.; Perteghella, S.; Torre, M.L.; Corsico, A.G. Mesenchymal Stromal Cell Secretome for Severe COVID-19 Infections: Premises for the Therapeutic Use. Cells 2020, 9, 924. [Google Scholar] [CrossRef] [Green Version]
- U.S. National Institutes of Health. 2019. Available online: https://clinicaltrials.gov (accessed on 8 April 2020).
- Canham, M.A.; Campbell, J.D.M.; Mountford, J.C. The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019. J. Transl. Med. 2020, 18, 1–15. [Google Scholar] [CrossRef]
- Khoury, M.; Cuenca, J.; Cruz, F.F.; Figueroa, F.E.; Rocco, P.R.M.; Weiss, D.J. Current status of cell-based therapies for respiratory virus infections: Applicability to COVID-19. Eur. Respir. J. 2020, 55, 2000858. [Google Scholar] [CrossRef] [Green Version]
- Sengupta, V.; Sengupta, S.; Lazo, A.; Woods, P.; Nolan, A.; Bremer, N. Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19. Stem Cells Dev. 2020, 29, 747–754. [Google Scholar] [CrossRef] [PubMed]
- Leng, Z.; Zhu, R.; Hou, W.; Feng, Y.; Yang, Y.; Han, Q.; Shan, G.; Meng, F.; Du, D.; Wang, S.; et al. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020, 11, 216–228. [Google Scholar] [CrossRef] [Green Version]
- NIH. A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia. Case Med Res. 2020. [Google Scholar] [CrossRef]
- Alzahrani, F.A.; Saadeldin, I.M.; Ahmad, A.; Kumar, D.; Azhar, E.I.; Siddiqui, A.J.; Kurdi, B.; Sajini, A.; Alrefaei, A.F.; Jahan, S. The Potential Use of Mesenchymal Stem Cells and Their Derived Exosomes as Immunomodulatory Agents for COVID-19 Patients. Stem Cells Int. 2020, 2020, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Pocsfalvi, G.; Mammadova, R.; Ramos Juarez, A.P.; Bokka, R.; Trepiccione, F.; Capasso, G. COVID-19 and Extracellular Vesicles: An Intriguing Interplay. Kidney Blood Press. Res. 2020, 45, 661–670. [Google Scholar] [CrossRef]
- Organicell Flow for Patients with COVID-19, NCT04384445. 2020. Available online: https://clinicaltrials.gov/show/NCT04384445 (accessed on 12 May 2020).
- Singh, S.; Chakravarty, T.; Chen, P.; Akhmerov, A.; Falk, J.; Friedman, O.; Zaman, T.; Ebinger, J.E.; Gheorghiu, M.; Marbán, L.; et al. Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: Compassionate-use case series. Basic Res. Cardiol. 2020, 115, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Pneumonia, NCT04491240. 2020. Available online: https://clinicaltrials.gov/show/NCT04491240 (accessed on 29 July 2020).
Viruses | Viral Cargo | Cellular Target | Exosome Biogenesis | Exosomes Roles in the Pathogenesis | Medical Usefulness and Applications | References |
---|---|---|---|---|---|---|
Adenovirus | mRNA and miRNA | dendritic cells | Developing of early endosome | Attaching of cell surface receptors onto host cells | The host body of HIV-1 inspires to be clear of viral factors by releasing them into exosomes | [15,77] |
HSV-1 | VP16, Heat shock proteins, HSV gB, ICP 127, miRNA | Epithelial cells | Trafficking proteins, DNA, RNA and lipids | Delivering of suppressed membrane protein 1 (LMP1) to host cells | Exosomes suppress or stimulate the immune response (immunomodulators) | [15,78,79,80,81,82,83] |
Ebola | DNA | macrophage, dendritic cells, | early endosome development | Cell surface receptors Attachment | Clearing the host bodies from virions | [84,85] |
EBV | RNA, miRNA, LMP1, 2A, gp350, EBERs | Lymphocytes | budding of endosomal multivesicular bodies | Proliferation, viral reactivation apoptosis, immune evasion | Intercellular communication between cells of the immune system | [86,87,88,89,90,91] |
HCV | miRNA, CD9, CD63, CD 81, HCV gRNA, RNA | Hepatocytes | receptor-mediated endocytosis, and plasma membrane fusion | viral maturation and immune evasion | Neutralizing antibodies are resistant to HCV transmission by exosomes as a potential immune evasion mechanism. | [92,93,94] |
Dengue virus | Immunoregulator molecules (MHCI and MCII) | Monocytes, macrophages | Recruit ESCRTs to the endosomal membrane | Assembly, transfer of viral RNAs, and suppression of immune activation. | Development of antiviral and vaccine candidate | [95] |
HPV | immunoregulator molecules, miRNA | Epithelial cells | ESCRTs are delivered to the site of budding | Apoptosis, viral proliferation, | Promoting anti-apoptotic potential. | [96] |
CMV | CMV gB | WBC, epithelial cells | Stimulating membrane budding | Improved viral pathogenicity, infection of myeloid dendritic cells | Inflammatory and regulatory markers | [97] |
polyomaviruses, (JCPyV and BKPyV) | Virion particles and miRNA | kidney, bone marrow, and central nervous system (CNS) | Virions packaged within EVs and associated to vesicles surface | play a key role in the dissemination and spread of polyomaviruses | Enhanced viral transmission and can be used as biomarker | [98,99,100,101] |
Coxsackievirus B1 | Replication competent genome within EV | Epithelial cells | Increased EV biogenesis | Increase viral spread | prolonged viral replication through micro RNA packaged in exosomes and can be used biomarker | [102] |
Chikungna virus | apoptotic bodies | Skeletal muscles, brain, and liver cells | hijacking apoptotic bodies | Infectious virions hijacking apoptotic bodies. Increased viral spread | Increased viral spread and can be used as biomarker | [103] |
ZIKV | Macrophage-derived exosomes | Brain, skin, placenta, retina, testis, and kidney cells | Infection significantly increases EV formation | Induction of placental proinflammatory cytokine production. | EVs derived from the semen of a ZIKV-infected patient inhibited ZIKV and delivering therapeutics across brain barriers | |
ZIKV NS5-mediated activation of NLRP3 | Activation of host inflammatory response and macrophage recruitment promotes inflammation | [104,105] | ||||
EV-bound ZIKV-RNA and E-protein | Increased ZIKV transmission across neurons | [106] | ||||
HIV | Cytoskeletal proteins (Actin, Tubulin, Lamin, Myosin)miRTAR, miRNA, Nef | Lymphocytes | ESCRT I and IIenhance membrane budding | Induce proinflammatory cytokines, inhibition of apoptosis, increased susceptibility of naïve T cells, downregulation of CD4 and MHC I, Support viral reproduction and pathogenesis | Analytical indicators in HIV-1, antiviral activity | [107,108,109,110,111] |
HBV | HBsAg, DNA, RNA | Hepatocytes | Multivesicular bodies fuse with the plasma membrane and secrete exosomes | Innate immunity evasion, transmission regulators | Drug delivery candidates for the targeted or systematic vehicle to particular organs or tissues | [14,112,113] |
HAV | HAV particles, enzymes, HAV gRNA, | Hepatocytes | Transport of ESCRT III, VPS4B, and ALIX. through endosomal-sorting complexes | Increasing viral infectivity, innate immunity evasion, intercellular communications | Drug delivery candidates for the targeted or systematic vehicle to particular organs or tissues | [114] |
Rift Valley fever virus | Viral proteins, miRNA, mRNA | WBC | ESCRTs enhance membrane budding | Immune evasion, apoptosis, enhance viral infectivity | Analytic indicators | [115] |
human T-lymphotropic virus | mRNA, miRNA, trans-activator protein | Lymphocytes | ESCRTs Stimulate membrane budding | Activate cytokines, damage to neurons, increase viral replication | Contribute to the pathology of the viral infection | [116,117,118] |
HHV-8 | RNA, miRNA | endothelial cells, WBC | budding of endosomal multivesicular bodies | cell metabolism, immune modulation | Intercellular communication between cells of the immune system | [119,120] |
Clinical Trials | Applied Therapy | Source | Route of Administration | Outcome/Aims | Ref |
---|---|---|---|---|---|
ChiCTR2000030484 | MSCs and EVs | MSCs derived from the human umbilical cord | Intravenous (IV) | Exploring the safety and efficacy of MSCs and EVs | [266] |
ChiCTR2000030261 | EVs | MSCs | Aerosol inhalation | Promoting early recovery and avoiding complications through enhancing immunity and inhibiting inflammatory factors | [268] |
NCT04389385 | EVs | Allogeneic COVID-19 specific T cells (CSTC) | Aerosol inhalation | Estimating the safety and efficiency of inhaled CSTC-exosomes in the treatment of early-stage pneumonia resulting from COVID-19 infection. | [269] |
NCT04276987 | EVs | MSCs derived from allogeneic adipose tissue | Aerosol inhalation | Exploring the safety and efficiency of inhaled EVs in the treatment of COVID-19 infection. | [270] |
NCT04493242 | EVs (ExofloTM) | MSCs derived from allogeneic bone marrow | IV | Exploring the safety and efficacy of EVs administrating intravenously as a treatment for ARDS | [271] |
NCT04338347 | EVs (CAP-1002) | Allogeneic cardiosphere derived cells | IV | Evaluating the safety and efficacy of EVs shed from allogeneic cardiosphere derived cells in the treatment of COVID-19 infection. | [272,273] |
NCT04491240 | EVs | MSCs | Aerosol inhalation | Estimating the safety and efficiency of exosome inhalation in the treatment of COVID-19 pneumonia | [274] |
NCT04384445 | HAF, containing EVs (OrganicellTM Flow) | Human amniotic fluid (HAF) | IV | Exploring the safety of HAF-derived acellular products and their efficacy as a therapeutic agent against COVID-19 infection. | [272] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Saad, M.H.; Badierah, R.; Redwan, E.M.; El-Fakharany, E.M. A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions. Pharmaceutics 2021, 13, 1405. https://doi.org/10.3390/pharmaceutics13091405
Saad MH, Badierah R, Redwan EM, El-Fakharany EM. A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions. Pharmaceutics. 2021; 13(9):1405. https://doi.org/10.3390/pharmaceutics13091405
Chicago/Turabian StyleSaad, Mabroka H., Raied Badierah, Elrashdy M. Redwan, and Esmail M. El-Fakharany. 2021. "A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions" Pharmaceutics 13, no. 9: 1405. https://doi.org/10.3390/pharmaceutics13091405
APA StyleSaad, M. H., Badierah, R., Redwan, E. M., & El-Fakharany, E. M. (2021). A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions. Pharmaceutics, 13(9), 1405. https://doi.org/10.3390/pharmaceutics13091405