Abstract
Retroviruses comprise an ancient and varied group of viruses with the unique ability to integrate DNA from an RNA transcript into the genome, a subset of which are able to integrate in humans. The timing of these integrations during human history has dictated whether these viruses have remained exogenous and given rise to various human diseases or have become inseparable from the host genome (endogenous retroviruses). Given the ability of retroviruses to integrate into the host and subsequently co-opt host cellular process for viral propagation, retroviruses have been shown to be closely associated with several cellular processes including exosome formation. Exosomes are 30-150 nm unilamellar extracellular vesicles that originate from intraluminal vesicles (ILVs) that form in the endosomal compartment. Exosomes have been shown to be important in intercellular communication and immune cell function. Almost every cell type studied has been shown to produce these types of vesicles, with the cell type dictating the contents, which include proteins, mRNA, and miRNAs. Importantly, recent evidence has shown that infection by viruses, including retroviruses, alter the contents and subsequent function of produced exosomes. In this review, we will discuss the important retroviruses associated with human health and disease. Furthermore, we will delve into the impact of exosome formation and manipulation by integrated retroviruses on human health, survival, and human retroviral disease pathogenesis.
Similar content being viewed by others
References
Aiewsakun P, Katzourakis A (2017) Marine origin of retroviruses in the early Palaeozoic era. Nat Commun 8:13954. https://doi.org/10.1038/ncomms13954
Alefantis T, Jain P, Ahuja J, Mostoller K, Wigdahl B (2005) HTLV-1 tax nucleocytoplasmic shuttling, interaction with the secretory pathway, extracellular signaling, and implications for neurologic disease. J Biomed Sci 12:961–974. https://doi.org/10.1007/s11373-005-9026-x
Alefantis T, Mostoller K, Jain P, Harhaj E, Grant C, Wigdahl B (2005) Secretion of the human T cell leukemia virus type I transactivator protein tax. J Biol Chem 280:17353–17362. https://doi.org/10.1074/jbc.M409851200
Alenquer M, Amorim MJ (2015) Exosome biogenesis, regulation, and function in viral infection. Viruses 7:5066–5083. https://doi.org/10.3390/v7092862
Alfahad T, Nath A (2013) Retroviruses and amyotrophic lateral sclerosis. Antivir Res 99:180–187. https://doi.org/10.1016/j.antiviral.2013.05.006
Ali SA, Huang MB, Campbell PE, Roth WW, Campbell T, Khan M, Newman G, Villinger F, Powell MD, Bond VC (2010) Genetic characterization of HIV type 1 Nef-induced vesicle secretion. AIDS Res Hum Retrovir 26:173–192. https://doi.org/10.1089/aid.2009.0068
Anderson MR, Enose-Akahata Y, Massoud R, Ngouth N, Tanaka Y, Oh U, Jacobson S (2014) Epigenetic modification of the FoxP3 TSDR in HAM/TSP decreases the functional suppression of Tregs. J NeuroImmune Pharmacol 9:522–532. https://doi.org/10.1007/s11481-014-9547-z
Anderson MR, Kashanchi F, Jacobson S (2016) Exosomes in viral disease. Neurotherapeutics 13:535–546. https://doi.org/10.1007/s13311-016-0450-6
Andreu Z, Yanez-Mo M (2014) Tetraspanins in extracellular vesicle formation and function. Front Immunol 5:442. https://doi.org/10.3389/fimmu.2014.00442
Arenaccio C, Anticoli S, Manfredi F, Chiozzini C, Olivetta E, Federico M (2015) Latent HIV-1 is activated by exosomes from cells infected with either replication-competent or defective HIV-1. Retrovirology 12:87. https://doi.org/10.1186/s12977-015-0216-y
Arenaccio C, Chiozzini C, Columba-Cabezas S, Manfredi F, Affabris E, Baur A, Federico M (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. https://doi.org/10.1128/JVI.01712-14
Arias M, Fan H (2014) The saga of XMRV: a virus that infects human cells but is not a human virus Emerg Microbes Infect 3:e doi:https://doi.org/10.1038/emi.2014.25
Baglio SR, Pegtel DM, Baldini N (2012) Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Front Physiol 3:359. https://doi.org/10.3389/fphys.2012.00359
Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14:677–685. https://doi.org/10.1038/ncb2502
Balaj L, Lessard R, Dai L, Cho YJ, Pomeroy SL, Breakefield XO, Skog J (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180. https://doi.org/10.1038/ncomms1180
Bangham CRM, Matsuoka M (2017) Human T-cell leukaemia virus type 1: parasitism and pathogenesis. Philos Trans R Soc Lond Ser B Biol Sci 372:20160272. https://doi.org/10.1098/rstb.2016.0272
Bannert N, Kurth R (2004) Retroelements and the human genome: new perspectives on an old relation. Proc Natl Acad Sci U S A 101(Suppl 2):14572–14579. https://doi.org/10.1073/pnas.0404838101
Baratella M, Forlani G, Raval GU, Tedeschi A, Gout O, Gessain A, Tosi G, Accolla RS (2017) Cytoplasmic localization of HTLV-1 HBZ protein: a biomarker of HTLV-1-associated myelopathy/tropical spastic Paraparesis (HAM/TSP). PLoS Negl Trop Dis 11:e0005285. https://doi.org/10.1371/journal.pntd.0005285
Barbulescu M, Turner G, Seaman MI, Deinard AS, Kidd KK, Lenz J (1999) Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans. Curr Biol 9:861–868
Bashratyan R, Regn D, Rahman MJ, Marquardt K, Fink E, Hu WY, Elder JH, Binley J, Sherman LA, Dai YD (2017) Type 1 diabetes pathogenesis is modulated by spontaneous autoimmune responses to endogenous retrovirus antigens in NOD mice. Eur J Immunol 47:575–584. https://doi.org/10.1002/eji.201646755
Bernard MA, Zhao H, Yue SC, Anandaiah A, Koziel H, Tachado SD (2014) Novel HIV-1 miRNAs stimulate TNFalpha release in human macrophages via TLR8 signaling pathway. PLoS One 9:e106006. https://doi.org/10.1371/journal.pone.0106006
Bissig C, Gruenberg J (2014) ALIX and the multivesicular endosome: ALIX in wonderland. Trends Cell Biol 24:19–25. https://doi.org/10.1016/j.tcb.2013.10.009
Campbell PE, Isayev O, Ali SA, Roth WW, Huang MB, Powell MD, Leszczynski J, Bond VC (2012) Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. J Mol Model 18:4603–4613. https://doi.org/10.1007/s00894-012-1452-x
Campbell TD, Khan M, Huang MB, Bond VC, Powell MD (2008) HIV-1 Nef protein is secreted into vesicles that can fuse with target cells and virions. Ethnicity & disease 18:S2–14-19
Cloyd MW (1996) Human Retroviruses. In: th, Baron S (eds) Medical Microbiology. Galveston (TX),
Colombo M, Raposo G, Thery C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289. https://doi.org/10.1146/annurev-cellbio-101512-122326
Columba Cabezas S, Federico M (2013) Sequences within RNA coding for HIV-1 gag p17 are efficiently targeted to exosomes. Cell Microbiol 15:412–429. https://doi.org/10.1111/cmi.12046
Cowan EP, Alexander RK, Daniel S, Kashanchi F, Brady JN (1997) Induction of tumor necrosis factor alpha in human neuronal cells by extracellular human T-cell lymphotropic virus type 1 tax. J Virol 71:6982–6989
Currer R, van Duyne R, Jaworski E, Guendel I, Sampey G, Das R, Narayanan A, Kashanchi F (2012) HTLV tax: a fascinating multifunctional co-regulator of viral and cellular pathways. Front Microbiol 3:406. https://doi.org/10.3389/fmicb.2012.00406
Dai YD, Sheng H, Dias P, Jubayer Rahman M, Bashratyan R, Regn D, Marquardt K (2017) Autoimmune responses to exosomes and candidate antigens contribute to type 1 diabetes in non-obese diabetic mice. Curr Diab Rep 17:130. https://doi.org/10.1007/s11892-017-0962-4
Das AT, Harwig A, Berkhout B (2011) The HIV-1 tat protein has a versatile role in activating viral transcription. J Virol 85:9506–9516. https://doi.org/10.1128/JVI.00650-11
de Carvalho JV, de Castro RO, da Silva EZM, Silveira PP, da Silva-Januário ME, Arruda E, Jamur MC, Oliver C, Aguiar RS, daSilva LLP (2014) Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection. PLoS One 9:e113691. https://doi.org/10.1371/journal.pone.0113691
Denner J (2010) Detection of a gammaretrovirus, XMRV, in the human population: open questions and implications for xenotransplantation. Retrovirology 7:16. https://doi.org/10.1186/1742-4690-7-16
Desfarges S, Ciuffi A (2010) Retroviral integration site selection. Viruses 2:111–130. https://doi.org/10.3390/v2010111
Dhib-Jalbut S, Hoffman PM, Yamabe T, Sun D, Xia J, Eisenberg H, Bergey G, Ruscetti FW (1994) Extracellular human T-cell lymphotropic virus type I tax protein induces cytokine production in adult human microglial cells. Ann Neurol 36:787–790. https://doi.org/10.1002/ana.410360516
Douville R, Liu J, Rothstein J, Nath A (2011) Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis. Ann Neurol 69:141–151. https://doi.org/10.1002/ana.22149
Douville RN, Nath A (2014) Human endogenous retroviruses and the nervous system. Handb Clin Neurol 123:465–485. https://doi.org/10.1016/B978-0-444-53488-0.00022-5
Downey RF, Sullivan FJ, Wang-Johanning F, Ambs S, Giles FJ, Glynn SA (2015) Human endogenous retrovirus K and cancer: innocent bystander or tumorigenic accomplice? Int J Cancer 137:1249–1257. https://doi.org/10.1002/ijc.29003
Ehrlich M (2009) DNA hypomethylation in cancer cells. Epigenomics 1:239–259. https://doi.org/10.2217/epi.09.33
Escalera-Zamudio M, Greenwood AD (2016) On the classification and evolution of endogenous retrovirus: human endogenous retroviruses may not be 'human' after all. APMIS 124:44–51. https://doi.org/10.1111/apm.12489
Fader CM, Sanchez DG, Mestre MB, Colombo MI (2009) TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta 1793:1901–1916. https://doi.org/10.1016/j.bbamcr.2009.09.011
Fang Y, Wu N, Gan X, Yan W, Morrell JC, Gould SJ (2007) Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol 5:e158. https://doi.org/10.1371/journal.pbio.0050158
Filipenko NR, MacLeod TJ, Yoon CS, Waisman DM (2004) Annexin A2 is a novel RNA-binding protein. J Biol Chem 279:8723–8731. https://doi.org/10.1074/jbc.M311951200
Fisher RD, Chung HY, Zhai Q, Robinson H, Sundquist WI, Hill CP (2007) Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. Cell 128:841–852. https://doi.org/10.1016/j.cell.2007.01.035
Garson JA, Tuke PW, Giraud P, Paranhos-Baccala G, Perron H (1998) Detection of virion-associated MSRV-RNA in serum of patients with multiple sclerosis. Lancet 351:33
Gimenez J, Montgiraud C, Pichon JP, Bonnaud B, Arsac M, Ruel K, Bouton O, Mallet F (2010) Custom human endogenous retroviruses dedicated microarray identifies self-induced HERV-W family elements reactivated in testicular cancer upon methylation control. Nucleic Acids Res 38:2229–2246. https://doi.org/10.1093/nar/gkp1214
Gonzalez-Cao M, Iduma P, Karachaliou N, Santarpia M, Blanco J, Rosell R (2016) Human endogenous retroviruses and cancer. Cancer Biol Med 13:483–488. https://doi.org/10.20892/j.issn.2095-3941.2016.0080
Gordon-Alonso M, Yanez-Mo M, Barreiro O, Alvarez S, Munoz-Fernandez MA, Valenzuela-Fernandez A, Sanchez-Madrid F (2006) Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion. J Immunol 177:5129–5137
Gould SJ, Booth AM, Hildreth JE (2003) The Trojan exosome hypothesis. Proc Natl Acad Sci U S A 100:10592–10597. https://doi.org/10.1073/pnas.1831413100
Grant C, Oh U, Yao K, Yamano Y, Jacobson S (2008) Dysregulation of TGF-beta signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease. Blood 111:5601–5609. https://doi.org/10.1182/blood-2007-11-123430
Griffiths DJ (2001) Endogenous retroviruses in the human genome sequence Genome Biol 2:REVIEWS1017
Hagiwara K, Katsuda T, Gailhouste L, Kosaka N, Ochiya T (2015) Commitment of Annexin A2 in recruitment of microRNAs into extracellular vesicles. FEBS Lett 589:4071–4078. https://doi.org/10.1016/j.febslet.2015.11.036
Han SP, Friend LR, Carson JH, Korza G, Barbarese E, Maggipinto M, Hatfield JT, Rothnagel JA, Smith R (2010) Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms. Traffic 11:886–898. https://doi.org/10.1111/j.1600-0854.2010.01072.x
Helwa I, Cai J, Drewry MD, Zimmerman A, Dinkins MB, Khaled ML, Seremwe M, Dismuke WM, Bieberich E, Stamer WD, Hamrick MW, Liu Y (2017) A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS One 12:e0170628. https://doi.org/10.1371/journal.pone.0170628
Henne WM, Buchkovich NJ, Emr SD (2011) The ESCRT pathway. Dev Cell 21:77–91. https://doi.org/10.1016/j.devcel.2011.05.015
Holder BS, Tower CL, Abrahams VM, Aplin JD (2012) Syncytin 1 in the human placenta. Placenta 33:460–466. https://doi.org/10.1016/j.placenta.2012.02.012
Hughes JF, Coffin JM (2005) Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome. Genetics 171:1183–1194. https://doi.org/10.1534/genetics.105.043976
Irish BP, Khan ZK, Jain P, Nonnemacher MR, Pirrone V, Rahman S, Rajagopalan N, Suchitra JB, Mostoller K, Wigdahl B (2009) Molecular mechanisms of neurodegenerative diseases induced by human retroviruses: a review. Am J Infect Dis 5:231–258
Izquierdo-Useros N, Puertas MC, Borras FE, Blanco J, Martinez-Picado J (2011) Exosomes and retroviruses: the chicken or the egg? Cell Microbiol 13:10–17. https://doi.org/10.1111/j.1462-5822.2010.01542.x
Jarrin I, Sellier P, Lopes A, Morgand M, Makovec T, Delcey V, Champion K, Simoneau G, Green A, Mouly S, Bergmann JF, Lloret-Linares C (2016) Etiologies and Management of Aseptic Meningitis in patients admitted to an internal medicine department. Medicine (Baltimore) 95:e2372. https://doi.org/10.1097/MD.0000000000002372
Jaworski E, Narayanan A, van Duyne R, Shabbeer-Meyering S, Iordanskiy S, Saifuddin M, Das R, Afonso PV, Sampey GC, Chung M, Popratiloff A, Shrestha B, Sehgal M, Jain P, Vertes A, Mahieux R, Kashanchi F (2014) Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain tax protein. J Biol Chem 289:22284–22305. https://doi.org/10.1074/jbc.M114.549659
Jaworski E, Saifuddin M, Sampey G, Shafagati N, van Duyne R, Iordanskiy S, Kehn-Hall K, Liotta L, Petricoin E, Young M, Lepene B, Kashanchi F (2014) The use of Nanotrap particles technology in capturing HIV-1 virions and viral proteins from infected cells. PLoS One 9:e96778. https://doi.org/10.1371/journal.pone.0096778
Jesus da Costa L, Lopes dos Santos A, Mandic R, Shaw K, Santana de Aguiar R, Tanuri A, Luciw PA, Peterlin BM (2009) Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication and progression to AIDS in rhesus macaques. Virology 394:47–56. https://doi.org/10.1016/j.virol.2009.08.024
Kannian P, Green PL (2010) Human T Lymphotropic virus type 1 (HTLV-1): molecular biology and oncogenesis. Viruses 2:2037–2077. https://doi.org/10.3390/v2092037
Kitamura T, Koshino Y, Shibata F, Oki T, Nakajima H, Nosaka T, Kumagai H (2003) Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp Hematol 31:1007–1014
Krementsov DN, Weng J, Lambele M, Roy NH, Thali M (2009) Tetraspanins regulate cell-to-cell transmission of HIV-1. Retrovirology 6:64. https://doi.org/10.1186/1742-4690-6-64
Kubota R, Nagai M, Kawanishi T, Osame M, Jacobson S (2000) Increased HTLV type 1 tax specific CD8+ cells in HTLV type 1-asociated myelopathy/tropical spastic paraparesis: correlation with HTLV type 1 proviral load. AIDS Res Hum Retrovir 16:1705–1709. https://doi.org/10.1089/08892220050193182
Lamparski HG, Metha-Damani A, Yao JY, Patel S, Hsu DH, Ruegg C, Le Pecq JB (2002) Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 270:211–226
Lenassi M, Cagney G, Liao M, Vaupotič T, Bartholomeeusen K, Cheng Y, Krogan NJ, Plemenitaš A, Peterlin BM (2010) HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic 11:110–122. https://doi.org/10.1111/j.1600-0854.2009.01006.x
Lepoutre V, Jain P, Quann K, Wigdahl B, Khan ZK (2009) Role of resident CNS cell populations in HTLV-1-associated neuroinflammatory disease. Front Biosci 14:1152–1168
Levin MC, Lee SM, Morcos Y, Brady J, Stuart J (2002) Cross-reactivity between immunodominant human T lymphotropic virus type I tax and neurons: implications for molecular mimicry. J Infect Dis 186:1514–1517. https://doi.org/10.1086/344734
Lezin A, Olindo S, Olière S, Varrin-Doyer M, Marlin R, Cabre P, Smadja D, Cesaire R (2005) Human T lymphotropic virus type I (HTLV-I) proviral load in cerebrospinal fluid: a new criterion for the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis? J Infect Dis 191:1830–1834. https://doi.org/10.1086/429962
Li HC, Fujiyoshi T, Lou H, Yashiki S, Sonoda S, Cartier L, Nunez L, Munoz I, Horai S, Tajima K (1999) The presence of ancient human T-cell lymphotropic virus type I provirus DNA in an Andean mummy. Nat Med 5:1428–1432. https://doi.org/10.1038/71006
Li M, Kesic M, Yin H, Yu L, Green PL (2009) Kinetic analysis of human T-cell leukemia virus type 1 gene expression in cell culture and infected animals. J Virol 83:3788–3797. https://doi.org/10.1128/JVI.02315-08
Lin J, Li J, Huang B, Liu J, Chen X, Chen XM, Xu YM, Huang LF, Wang XZ (2015) Exosomes: novel biomarkers for clinical diagnosis. Sci World J 2015:657086. https://doi.org/10.1155/2015/657086
Lokossou AG, Toudic C, Barbeau B (2014) Implication of human endogenous retrovirus envelope proteins in placental functions. Viruses 6:4609–4627. https://doi.org/10.3390/v6114609
Longatti A, Boyd B, Chisari FV (2015) Virion-independent transfer of replication-competent hepatitis C virus RNA between permissive cells. J Virol 89:2956–2961. https://doi.org/10.1128/JVI.02721-14
Luo X, Fan Y, Park IW, He JJ (2015) Exosomes are unlikely involved in intercellular Nef transfer. PLoS One 10:e0124436. https://doi.org/10.1371/journal.pone.0124436
Madison MN, Okeoma CM (2015) Exosomes: implications in HIV-1 pathogenesis. Viruses 7:4093–4118. https://doi.org/10.3390/v7072810
Malassine A, Frendo JL, Blaise S, Handschuh K, Gerbaud P, Tsatsaris V, Heidmann T, Evain-Brion D (2008) Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta. Retrovirology 5:6. https://doi.org/10.1186/1742-4690-5-6
Mameli G, Astone V, Arru G, Marconi S, Lovato L, Serra C, Sotgiu S, Bonetti B, Dolei A (2007) Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not human herpesvirus 6. Journal Gen Virol 88:264–274. https://doi.org/10.1099/vir.0.81890-0
Mansky LM (2000) In vivo analysis of human T-cell leukemia virus type 1 reverse transcription accuracy. J Virol 74:9525–9531
Matsuo H, Chevallier J, Mayran N, le Blanc I, Ferguson C, Fauré J, Blanc NS, Matile S, Dubochet J, Sadoul R, Parton RG, Vilbois F, Gruenberg J (2004) Role of LBPA and Alix in multivesicular liposome formation and endosome. Organization. Science 303:531–534. https://doi.org/10.1126/science.1092425
Meckes DG Jr, Raab-Traub N (2011) Microvesicles and viral infection. J Virol 85:12844–12854. https://doi.org/10.1128/JVI.05853-11
Mi S, Lee X, Li XP, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC, McCoy JM (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403:785–789. https://doi.org/10.1038/35001608
Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, González MÁ, Bernad A, Sánchez-Madrid F (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2:282. https://doi.org/10.1038/ncomms1285
Mittelbrunn M, Sanchez-Madrid F (2012) Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol 13:328–335. https://doi.org/10.1038/nrm3335
Morandi E, Tanasescu R, Tarlinton RE, Constantinescu CS, Zhang W, Tench C, Gran B (2017) The association between human endogenous retroviruses and multiple sclerosis: a systematic review and meta-analysis. PLoS One 12:e0172415. https://doi.org/10.1371/journal.pone.0172415
Morandi E, Tarlinton RE, Gran B (2015) Multiple sclerosis between genetics and infections: human endogenous retroviruses in monocytes and macrophages. Front Immunol 6:647. https://doi.org/10.3389/fimmu.2015.00647
Narayanan A, Iordanskiy S, Das R, van Duyne R, Santos S, Jaworski E, Guendel I, Sampey G, Dalby E, Iglesias-Ussel M, Popratiloff A, Hakami R, Kehn-Hall K, Young M, Subra C, Gilbert C, Bailey C, Romerio F, Kashanchi F (2013) Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. J Biol Chem 288:20014–20033. https://doi.org/10.1074/jbc.M112.438895
Nexo BA, Jensen SB, Hansen B, Laska MJ (2016) Endogenous retroviruses are associated with autoimmune diseases Ugeskr Laeger 178
Nexo BA et al (2016) Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci. Immunol Res 64:55–63. https://doi.org/10.1007/s12026-015-8671-z
Noorali S, Rotar IC, Lewis C, Pestaner JP, Pace DG, Sison A, Bagasra O (2009) Role of HERV-W syncytin-1 in placentation and maintenance of human pregnancy. Appl Immunohistochem Mol Morphol 17:319–328. https://doi.org/10.1097/PAI.0b013e31819640f9
Nour AM, Modis Y (2014) Endosomal vesicles as vehicles for viral genomes. Trends Cell Biol 24:449–454. https://doi.org/10.1016/j.tcb.2014.03.006
Novak K (1999) Ancient HTLV-1. Nat Med 5:1357. https://doi.org/10.1038/70923
Nowak J, Januszkiewicz D, Pernak M, Liweń I, Zawada M, Rembowska J, Nowicka K, Lewandowski K, Hertmanowska H, Wender M (2003) Multiple sclerosis-associated virus-related pol sequences found both in multiple sclerosis and healthy donors are more frequently expressed in multiple sclerosis patients. J Neurovirol 9:112–117. https://doi.org/10.1080/13550280390173355
Okoye IS, Coomes SM, Pelly VS, Czieso S, Papayannopoulos V, Tolmachova T, Seabra MC, Wilson MS (2014) MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 41:89–103. https://doi.org/10.1016/j.immuni.2014.05.019
Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12:19–30; sup pp 11–13 doi:https://doi.org/10.1038/ncb2000
Pelchen-Matthews A, Kramer B, Marsh M (2003) Infectious HIV-1 assembles in late endosomes in primary macrophages. J Cell Biol 162:443–455. https://doi.org/10.1083/jcb.200304008
Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, López-Martín S, Ursa A, Sánchez-Madrid F, Vázquez J, Yáñez-Mó M (2013) The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J Biol Chem 288:11649–11661. https://doi.org/10.1074/jbc.M112.445304
Perez-Hernandez J, Cortes R (2015) Extracellular Vesicles as Biomarkers of Systemic Lupus Erythematosus. Dis Markers 2015:613536. https://doi.org/10.1155/2015/613536
Perron H, Germi R, Bernard C, Garcia-Montojo M, Deluen C, Farinelli L, Faucard R, Veas F, Stefas I, Fabriek BO, van-Horssen J, van-der-Valk P, Gerdil C, Mancuso R, Saresella M, Clerici M, Marcel S, Creange A, Cavaretta R, Caputo D, Arru G, Morand P, Lang AB, Sotgiu S, Ruprecht K, Rieckmann P, Villoslada P, Chofflon M, Boucraut J, Pelletier J, Hartung HP (2012) Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Mult Scler 18:1721–1736. https://doi.org/10.1177/1352458512441381
Piguet V, Steinman RM (2007) The interaction of HIV with dendritic cells: outcomes and pathways. Trends Immunol 28:503–510. https://doi.org/10.1016/j.it.2007.07.010
Potgens AJ, Drewlo S, Kokozidou M, Kaufmann P (2004) Syncytin: the major regulator of trophoblast fusion? Recent developments and hypotheses on its action. Hum Reprod Update 10:487–496. https://doi.org/10.1093/humupd/dmh039
Properzi F, Logozzi M, Fais S (2013) Exosomes: the future of biomarkers in medicine. Biomark Med 7:769–778. https://doi.org/10.2217/bmm.13.63
Ramakrishnaiah V, Thumann C, Fofana I, Habersetzer F, Pan Q, de Ruiter PE, Willemsen R, Demmers JAA, Stalin Raj V, Jenster G, Kwekkeboom J, Tilanus HW, Haagmans BL, Baumert TF, van der Laan LJW (2013) Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc Natl Acad Sci U S A 110:13109–13113. https://doi.org/10.1073/pnas.1221899110
Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383. https://doi.org/10.1083/jcb.201211138
Rende F, Cavallari I, Corradin A, Silic-Benussi M, Toulza F, Toffolo GM, Tanaka Y, Jacobson S, Taylor GP, D'Agostino DM, Bangham CRM, Ciminale V (2011) Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNAs. Blood 117:4855–4859. https://doi.org/10.1182/blood-2010-11-316463
Retrovidae (2012). In: King A, Lefkowitz E, Adams MJ, Carstens EB (ed) Virus Taxonomy. Ninth Report of the International Committee on Taxonomy of Viruses edn. Elsevier, pp 477–495
Rider MA, Hurwitz SN, Meckes DG Jr (2016) ExtraPEG: a polyethylene glycol-based method for enrichment of extracellular vesicles. Sci Rep 6:23978. https://doi.org/10.1038/srep23978
Robbins PD, Morelli AE (2014) Regulation of immune responses by extracellular vesicles. Nat Rev Immunol 14:195–208. https://doi.org/10.1038/nri3622
Romanelli MG, Diani E, Bergamo E, Casoli C, Ciminale V, Bex F, Bertazzoni U (2013) Highlights on distinctive structural and functional properties of HTLV tax proteins. Front Microbiol 4:271. https://doi.org/10.3389/fmicb.2013.00271
Roucourt B, Meeussen S, Bao J, Zimmermann P, David G (2015) Heparanase activates the syndecan-syntenin-ALIX exosome pathway. Cell Res 25:412–428. https://doi.org/10.1038/cr.2015.29
Ryan FP (2004) Human endogenous retroviruses in health and disease: a symbiotic perspective. J R Soc Med 97:560–565. https://doi.org/10.1258/jrsm.97.12.560
Ryan FP (2011) Human endogenous retroviruses in multiple sclerosis: potential for novel neuro-pharmacological research. Curr Neuropharmacol 9:360–369. https://doi.org/10.2174/157015911795596568
Sampey GC, Meyering SS, Asad Zadeh M, Saifuddin M, Hakami RM, Kashanchi F (2014) Exosomes and their role in CNS viral infections. J Neurovirol 20:199–208. https://doi.org/10.1007/s13365-014-0238-6
Sampey GC, Saifuddin M, Schwab A, Barclay R, Punya S, Chung MC, Hakami RM, Asad Zadeh M, Lepene B, Klase ZA, el-Hage N, Young M, Iordanskiy S, Kashanchi F (2016) Exosomes from HIV-1-infected cells stimulate production of pro-inflammatory cytokines through trans-activating response (TAR) RNA. J Biol Chem 291:1251–1266. https://doi.org/10.1074/jbc.M115.662171
Savina A, Fader CM, Damiani MT, Colombo MI (2005) Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner. Traffic 6:131–143. https://doi.org/10.1111/j.1600-0854.2004.00257.x
Schmidt O, Teis D (2012) The ESCRT machinery. Curr Biol 22:R116–R120. https://doi.org/10.1016/j.cub.2012.01.028
Schorey JS, Cheng Y, Singh PP, Smith VL (2015) Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep 16:24–43. https://doi.org/10.15252/embr.201439363
Schulz WA, Steinhoff C, Florl AR (2006) Methylation of endogenous human retroelements in health and disease. Curr Top Microbiol Immunol 310:211–250
Serrao E, Engelman AN (2016) Sites of retroviral DNA integration: from basic research to clinical applications. Crit Rev Biochem Mol Biol 51:26–42. https://doi.org/10.3109/10409238.2015.1102859
Sharp PM, Hahn BH (2011) Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med 1:a006841. https://doi.org/10.1101/cshperspect.a006841
Shembade N, Harhaj EW (2010) Role of post-translational modifications of HTLV-1 tax in NF-kappaB activation. World J Biol Chem 1:13–20. https://doi.org/10.4331/wjbc.v1.i1.13
Shen B, Wu N, Yang JM, Gould SJ (2011) Protein targeting to exosomes/microvesicles by plasma membrane anchors. J Biol Chem 286:14383–14395. https://doi.org/10.1074/jbc.M110.208660
Stengel S, Fiebig U, Kurth R, Denner J (2010) Regulation of human endogenous retrovirus-K expression in melanomas by CpG methylation. Genes Chromosomes Cancer 49:401–411. https://doi.org/10.1002/gcc.20751
Stoorvogel W (2015) Resolving sorting mechanisms into exosomes. Cell Res 25:531–532. https://doi.org/10.1038/cr.2015.39
Stuffers S, Sem Wegner C, Stenmark H, Brech A (2009) Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 10:925–937. https://doi.org/10.1111/j.1600-0854.2009.00920.x
Subramanian RP, Wildschutte JH, Russo C, Coffin JM (2011) Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses. Retrovirology 8:90. https://doi.org/10.1186/1742-4690-8-90
Sundquist WI, Krausslich HG (2012) HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med 2:a006924. https://doi.org/10.1101/cshperspect.a006924
Swaminathan G, Navas-Martin S, Martin-Garcia J (2014) MicroRNAs and HIV-1 infection: antiviral activities and beyond. J Mol Biol 426:1178–1197. https://doi.org/10.1016/j.jmb.2013.12.017
Tamai K, Tanaka N, Nakano T, Kakazu E, Kondo Y, Inoue J, Shiina M, Fukushima K, Hoshino T, Sano K, Ueno Y, Shimosegawa T, Sugamura K (2010) Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem Biophys Res Commun 399:384–390. https://doi.org/10.1016/j.bbrc.2010.07.083
Thali M (2009) The roles of tetraspanins in HIV-1 replication. Curr Top Microbiol Immunol 339:85–102. https://doi.org/10.1007/978-3-642-02175-6_5
Thali M (2011) Tetraspanin functions during HIV-1 and influenza virus replication. Biochem Soc Trans 39:529–531. https://doi.org/10.1042/BST0390529
Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brugger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247. https://doi.org/10.1126/science.1153124
Tremblay MJ, Fortin JF, Cantin R (1998) The acquisition of host-encoded proteins by nascent HIV-1. Immunol Today 19:346–351
Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ, Infectious Diseases Society of America (2008) The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis : An Official Publication of the Infectious Diseases Society of America 47:303–327. https://doi.org/10.1086/589747
Urbanelli L, Magini A, Buratta S, Brozzi A, Sagini K, Polchi A, Tancini B, Emiliani C (2013) Signaling pathways in exosomes biogenesis, secretion and fate. Genes (Basel) 4:152–170. https://doi.org/10.3390/genes4020152
van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G (2011) The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell 21:708–721. https://doi.org/10.1016/j.devcel.2011.08.019
Vargas A, Zhou S, Ethier-Chiasson M, Flipo D, Lafond J, Gilbert C, Barbeau B (2014) Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia. FASEB J 28:3703–3719. https://doi.org/10.1096/fj.13-239053
Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E (2007) Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis 7:266–281. https://doi.org/10.1016/S1473-3099(07)70081-6
Verweij FJ, van Eijndhoven MAJ, Hopmans ES, Vendrig T, Wurdinger T, Cahir-McFarland E, Kieff E, Geerts D, van der Kant R, Neefjes J, Middeldorp JM, Pegtel DM (2011) LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-kappaB activation. EMBO J 30:2115–2129. https://doi.org/10.1038/emboj.2011.123
Villarroya-Beltri C, Baixauli F, Gutierrez-Vazquez C, Sanchez-Madrid F, Mittelbrunn M (2014) Sorting it out: regulation of exosome loading. Semin Cancer Biol 28:3–13. https://doi.org/10.1016/j.semcancer.2014.04.009
Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, Pérez-Hernández D, Vázquez J, Martin-Cofreces N, Martinez-Herrera DJ, Pascual-Montano A, Mittelbrunn M, Sánchez-Madrid F (2013) Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 4:2980. https://doi.org/10.1038/ncomms3980
Wiley RD, Gummuluru S (2006) Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proc Natl Acad Sci U S A 103:738–743. https://doi.org/10.1073/pnas.0507995103
Yamano Y, Takenouchi N, Li HC, Tomaru U, Yao K, Grant CW, Maric DA, Jacobson S (2005) Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease. J Clin Invest 115:1361–1368. https://doi.org/10.1172/JCI23913
Yelamanchili SV, Lamberty BG, Rennard DA, Morsey BM, Hochfelder CG, Meays BM, Levy E, Fox HS (2015) MiR-21 in extracellular vesicles leads to neurotoxicity via TLR7 signaling in SIV neurological disease. PLoS Pathog 11:e1005032. https://doi.org/10.1371/journal.ppat.1005032
Zeringer E, Barta T, Li M, Vlassov AV (2015) Strategies for isolation of exosomes. Cold Spring Harb Protoc 2015:319–323. https://doi.org/10.1101/pdb.top074476
Zhang J, Li S, Li L, Li M, Guo C, Yao J, Mi S (2015) Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics 13:17–24. https://doi.org/10.1016/j.gpb.2015.02.001
Zhou L, Miranda-Saksena M, Saksena NK (2013) Viruses and neurodegeneration. Virol J 10:172. https://doi.org/10.1186/1743-422X-10-172
Funding
Studies involving HTLV-1 were funded internally by NINDS.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Anderson M declares that she has no conflicts of interest. Kashanchi F declares that he has no conflicts of interest. Jacobson S declares that he has no conflicts of interest.
Human and Animal Rights and Informed Consent
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consents were obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Anderson, M., Kashanchi, F. & Jacobson, S. Role of Exosomes in Human Retroviral Mediated Disorders. J Neuroimmune Pharmacol 13, 279–291 (2018). https://doi.org/10.1007/s11481-018-9784-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11481-018-9784-7