Extracellular vesicles and viruses: Are they close relatives?

Extracellular vesicles (EVs) released by various cells are small phospholipid membrane-enclosed entities that can carry miRNA. They are now central to research in many fields of biology because they seem to constitute a new system of cell–cell communication. Physical and chemical characteristics of many EVs, as well as their biogenesis pathways, resemble those of retroviruses. Moreover, EVs generated by virus-infected cells can incorporate viral proteins and fragments of viral RNA, being thus indistinguishable from defective (noninfectious) retroviruses. EVs, depending on the proteins and genetic material incorporated in them, play a significant role in viral infection, both facilitating and suppressing it. Deciphering the mechanisms of EV-cell interactions may facilitate the design of EVs that inhibit viral infection and can be used as vehicles for targeted drug delivery.

[1]  T. Wurdinger,et al.  Sensing of latent EBV infection through exosomal transfer of 5′pppRNA , 2016, Proceedings of the National Academy of Sciences.

[2]  V. Bond,et al.  Isolation of Exosomes from the Plasma of HIV-1 Positive Individuals. , 2016, Journal of visualized experiments : JoVE.

[3]  Gary K. Schwartz,et al.  Tumour exosome integrins determine organotropic metastasis , 2015, Nature.

[4]  P. Borrow,et al.  Viruses transfer the antiviral second messenger cGAMP between cells , 2015, Science.

[5]  G. Kroemer,et al.  Transmission of innate immune signaling by packaging of cGAMP in viral particles , 2015, Science.

[6]  J. McLinden,et al.  Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein Independently Inhibit T Cell Activation , 2015, PLoS pathogens.

[7]  G. Raposo,et al.  Extracellular vesicles shuffling intercellular messages: for good or for bad. , 2015, Current opinion in cell biology.

[8]  X. Bao,et al.  Exosomes and Their Role in the Life Cycle and Pathogenesis of RNA Viruses , 2015, Viruses.

[9]  Jacco van Rheenen,et al.  In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior , 2015, Cell.

[10]  J. Grivel,et al.  Antigenic composition of single nano-sized extracellular blood vesicles. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[11]  D. Meckes Exosomal Communication Goes Viral , 2015, Journal of Virology.

[12]  Joshua N Leonard,et al.  Therapeutic applications of extracellular vesicles: clinical promise and open questions. , 2015, Annual review of pharmacology and toxicology.

[13]  L. O’Driscoll,et al.  Biological properties of extracellular vesicles and their physiological functions , 2015, Journal of extracellular vesicles.

[14]  C. Oliver,et al.  Nef Neutralizes the Ability of Exosomes from CD4+ T Cells to Act as Decoys during HIV-1 Infection , 2014, PloS one.

[15]  C. Théry,et al.  Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. , 2014, Annual review of cell and developmental biology.

[16]  K. Kodys,et al.  Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90 , 2014, PLoS pathogens.

[17]  B. Ylstra,et al.  Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. , 2014, Cell reports.

[18]  M. Yáñez-Mó,et al.  Tetraspanins in Extracellular Vesicle Formation and Function , 2014, Front. Immunol..

[19]  Hui Zhao,et al.  Novel HIV-1 MiRNAs Stimulate TNFα Release in Human Macrophages via TLR8 Signaling Pathway , 2014, PloS one.

[20]  F. Dumas,et al.  Membrane organization of virus and target cell plays a role in HIV entry , 2014, Biochimie.

[21]  Clotilde Théry,et al.  Biogenesis and secretion of exosomes. , 2014, Current opinion in cell biology.

[22]  C. Chiozzini,et al.  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 , 2014, Journal of Virology.

[23]  A. Falus,et al.  Emerging role of extracellular vesicles in inflammatory diseases , 2014, Nature Reviews Rheumatology.

[24]  P. Altevogt,et al.  Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation , 2014, Journal of Neuroimmunology.

[25]  M. Tewari,et al.  Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions , 2014, Nucleic acids research.

[26]  P. Robbins,et al.  Regulation of immune responses by extracellular vesicles , 2014, Nature Reviews Immunology.

[27]  F. Sánchez‐Madrid,et al.  Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs , 2013, Nature Communications.

[28]  D. Stolz,et al.  Human placental trophoblasts confer viral resistance to recipient cells , 2013, Proceedings of the National Academy of Sciences.

[29]  Arsen O Batagov,et al.  Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3′-untranslated regions , 2013, Biology Direct.

[30]  X. Chen,et al.  microRNAs are ligands of Toll-like receptors. , 2013, RNA.

[31]  M. Young,et al.  Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA* , 2013, The Journal of Biological Chemistry.

[32]  F. Hu,et al.  A pathogenic picornavirus acquires an envelope by hijacking cellular membranes , 2013, Nature.

[33]  Graça Raposo,et al.  Extracellular vesicles: Exosomes, microvesicles, and friends , 2013, The Journal of cell biology.

[34]  F. Chisari,et al.  Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity. , 2012, Cell host & microbe.

[35]  H. Buermans,et al.  Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions , 2012, Nucleic acids research.

[36]  Ger J.A. Arkesteijn,et al.  Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles , 2011, Nanomedicine: Nanotechnology, Biology and Medicine.

[37]  Syed A. Ali,et al.  Secretion Modification Region-Derived Peptide Disrupts HIV-1 Nef's Interaction with Mortalin and Blocks Virus and Nef Exosome Release , 2011, Journal of Virology.

[38]  N. Raab-Traub,et al.  Microvesicles and Viral Infection , 2011, Journal of Virology.

[39]  A. Burlingame,et al.  HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. , 2010, Molecular cell.

[40]  G. Cagney,et al.  HIV Nef is Secreted in Exosomes and Triggers Apoptosis in Bystander CD4+ T Cells , 2010, Traffic.

[41]  L. Margolis,et al.  War and peace between microbes: HIV-1 interactions with coinfecting viruses. , 2009, Cell host & microbe.

[42]  E. C. Snow,et al.  Faculty Opinions recommendation of HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits. , 2009 .

[43]  Willem Stoorvogel,et al.  Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. , 2009, Blood.

[44]  H. Taylor,et al.  Exosomes Packaging APOBEC3G Confer Human Immunodeficiency Virus Resistance to Recipient Cells , 2008, Journal of Virology.

[45]  N. Maeda,et al.  Oncogenesis by retroviruses: old and new paradigms , 2008, Reviews in medical virology.

[46]  C. Gilbert,et al.  Discrimination between exosomes and HIV-1: purification of both vesicles from cell-free supernatants. , 2008, Journal of immunological methods.

[47]  Yuetsu Tanaka,et al.  Modulation of Human Immunodeficiency Virus Type 1 Infectivity through Incorporation of Tetraspanin Proteins , 2007, Journal of Virology.

[48]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[49]  M. Record,et al.  Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. , 2007, Biochimie.

[50]  W. Greene,et al.  Newly Synthesized APOBEC3G Is Incorporated into HIV Virions, Inhibited by HIV RNA, and Subsequently Activated by RNase H , 2007, PLoS pathogens.

[51]  C. Théry,et al.  ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. , 2005, Blood.

[52]  G. Raposo,et al.  Endosomes, exosomes and Trojan viruses. , 2004, Trends in microbiology.

[53]  M. Kozlov,et al.  Protein-lipid interplay in fusion and fission of biological membranes. , 2003, Annual review of biochemistry.

[54]  A. Booth,et al.  The Trojan exosome hypothesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[55]  M. Malim,et al.  DNA Deamination Mediates Innate Immunity to Retroviral Infection , 2003, Cell.

[56]  M. Ratajczak,et al.  Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV , 2003, AIDS.

[57]  C. Théry,et al.  Indirect activation of naïve CD4+ T cells by dendritic cell–derived exosomes , 2002, Nature Immunology.

[58]  R. North,et al.  Rapid secretion of interleukin-1β by microvesicle shedding , 2001 .

[59]  J. Lifson,et al.  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 , 2001, Journal of Virology.

[60]  R. North,et al.  Rapid secretion of interleukin-1beta by microvesicle shedding. , 2001, Immunity.

[61]  H. Brühl,et al.  Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection , 2000, Nature Medicine.

[62]  C. Melief,et al.  B lymphocytes secrete antigen-presenting vesicles , 1996, The Journal of experimental medicine.

[63]  R. Eckner,et al.  Defective Friend Spleen Focus-Forming Virus: Interfering Properties and Isolation Free from Standard Leukemia-Inducing Helper Virus , 1977, Journal of virology.

[64]  A. Huang,et al.  Defective interfering viruses. , 1973, Annual review of microbiology.