{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:34:34Z","timestamp":1792676074019,"version":"4.5.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T00:00:00Z","timestamp":1484179200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T00:00:00Z","timestamp":1484179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human immunodeficiency virus-associated neurological disorders (HANDs) affect the majority of AIDS patients and are a significant problem among HIV-1-infected individuals who live longer because of combined anti-retroviral therapies. HIV-1 utilizes a number of viral proteins and subsequent cytokine inductions to unleash its toxicity on neurons. Among HIV-1 viral proteins, Nef is a small protein expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HAND. In order to explore its effect in the central nervous system, HIV-1 Nef was expressed in primary human fetal astrocytes (PHFAs) using an adenovirus. Our results revealed that HIV-1 Nef is released in extracellular vesicles (EVs) derived from PHFA cells expressing the protein. Interestingly, HIV-1 Nef release in EVs was enriched significantly when the cells were treated with autophagy activators perifosine, tomaxifen, MG-132, and autophagy inhibitors LY294002 and wortmannin suggesting a novel role of autophagy signaling in HIV-1 Nef release from astrocytes. Next, Nef-carrying EVs were purified from astrocyte cultures and neurotoxic effects on neurons were analyzed. We observed that HIV-1 Nef-containing EVs were readily taken up by neurons as demonstrated by immunocytochemistry and immunoblotting. Furthermore, treatment of neurons with Nef-carrying EVs induced oxidative stress as evidenced by a decrease in glutathione levels. To further investigate its neurotoxic effects, we expressed HIV-1 Nef in primary neurons by adenoviral transduction. Intracellular expression of HIV-1 Nef caused axonal and neurite degeneration of neurons. Furthermore, expression of HIV-1 Nef decreased the levels of phospho-tau while enhancing total tau in primary neurons. In addition, treatment of primary neurons with Nef-carrying EVs suppressed functional neuronal action potential assessed by multielectrode array studies. Collectively, these data suggested that HIV-1 Nef can be a formidable contributor to neurotoxicity along with other factors, which leads to HAND in HIV-1-infected AIDS patients.<\/jats:p>","DOI":"10.1038\/cddis.2016.467","type":"journal-article","created":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T08:47:21Z","timestamp":1484210841000},"page":"e2542-e2542","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity"],"prefix":"10.1038","volume":"8","author":[{"given":"A","family":"Sami Saribas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Cicalese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha Mohseni","family":"Ahooyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Khalili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohreh","family":"Amini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilker Kudret","family":"Sariyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,12]]},"reference":[{"key":"BFcddis2016467_CR1","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1146\/annurev.micro.50.1.825","volume":"50","author":"G Pantaleo","year":"1996","unstructured":"Pantaleo G, Fauci AS . Immunopathogenesis of HIV infection. Annu Rev Microbiol 1996; 50: 825\u2013854.","journal-title":"Annu Rev Microbiol"},{"key":"BFcddis2016467_CR2","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1146\/annurev-pathol-011110-130254","volume":"6","author":"S Moir","year":"2011","unstructured":"Moir S, Chun TW, Fauci AS . Pathogenic mechanisms of HIV disease. Annu Rev Pathol Mech Dis 2011; 6: 223\u2013248.","journal-title":"Annu Rev Pathol Mech Dis"},{"key":"BFcddis2016467_CR3","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1126\/science.1243727","volume":"343","author":"C Fraser","year":"2014","unstructured":"Fraser C, Lythgoe K, Leventhal GE, Shirreff G, Hollingsworth TD, Alizon S . Bonhoeffer SVirulence and pathogenesis of HIV-1 infection: an evolutionary perspective. Science 2014; 343: 6177.","journal-title":"Science"},{"key":"BFcddis2016467_CR4","doi-asserted-by":"publisher","first-page":"7089","DOI":"10.1073\/pnas.83.18.7089","volume":"83","author":"CA Wiley","year":"1986","unstructured":"Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB . Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 1986; 83: 7089\u20137093.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2016467_CR5","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1126\/science.3277272","volume":"239","author":"RW Price","year":"1988","unstructured":"Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P . The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 1988; 239: 586\u2013592.","journal-title":"Science"},{"key":"BFcddis2016467_CR6","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1002\/jlb.65.4.453","volume":"65","author":"LG Epstein","year":"1999","unstructured":"Epstein LG, Gelbard HA . HIV-1-induced neuronal injury in the developing brain. J Leukoc Biol 1999; 65: 453\u2013457.","journal-title":"J Leukoc Biol"},{"key":"BFcddis2016467_CR7","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1146\/annurev.neuro.25.112701.142822","volume":"25","author":"KC Williams","year":"2002","unstructured":"Williams KC, Hickey WF . Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu Rev Neurosci 2002; 25: 537\u2013562.","journal-title":"Annu Rev Neurosci"},{"key":"BFcddis2016467_CR8","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.virusres.2005.04.009","volume":"111","author":"S Kramer-H\u00e4mmerle","year":"2005","unstructured":"Kramer-H\u00e4mmerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R . Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res 2005; 111: 194\u2013213.","journal-title":"Virus Res"},{"key":"BFcddis2016467_CR9","doi-asserted-by":"publisher","first-page":"e16659","DOI":"10.1371\/journal.pone.0016659","volume":"6","author":"SL Lamers","year":"2011","unstructured":"Lamers SL, Poon AF, McGrath MS . HIV-1 nef protein structures associated with brain infection and dementia pathogenesis. PLoS One 2011; 6: e16659.","journal-title":"PLoS One"},{"key":"BFcddis2016467_CR10","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1212\/WNL.0b013e31828c2e9e","volume":"80","author":"P Desplats","year":"2013","unstructured":"Desplats P, Dumaop W, Smith D, Adame A, Everall I, Letendre S et al. Molecular and pathologic insights from latent HIV-1 infection in the human brain. Neurology 2013; 80: 1415\u20131423.","journal-title":"Neurology"},{"key":"BFcddis2016467_CR11","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1128\/CMR.6.4.339","volume":"6","author":"WJ Atwood","year":"1993","unstructured":"Atwood WJ, Berger JR, Kaderman R, Tornatore CS, Major EO . Human immunodeficiency virus type 1 infection of the brain. Clin Microbiol Rev 1993; 6: 339\u2013366.","journal-title":"Clin Microbiol Rev"},{"key":"BFcddis2016467_CR12","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1097\/QAD.0000000000000553","volume":"29","author":"AK Bryant","year":"2015","unstructured":"Bryant AK, Ellis RJ, Umlauf A, Gouaux B, Soontornniyomkij V, Letendre SL et al. Antiretroviral therapy reduces neurodegeneration in HIV infection. AIDS 2015; 29: 323\u2013330.","journal-title":"AIDS"},{"key":"BFcddis2016467_CR13","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s11904-014-0255-3","volume":"12","author":"Z Zayyad","year":"2015","unstructured":"Zayyad Z, Spudich S . Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV\/AIDS Rep 2015; 12: 16\u201324.","journal-title":"Curr HIV\/AIDS Rep"},{"key":"BFcddis2016467_CR14","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1055\/s-0034-1372337","volume":"34","author":"RW Price","year":"2014","unstructured":"Price RW, Spudich SS, Peterson J, Joseph S, Fuchs D, Zetterberg H et al. Evolving character of chronic central nervous system HIV infection. Semin Neurol 2014; 34: 7\u201313.","journal-title":"Semin Neurol"},{"key":"BFcddis2016467_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00002030-199901140-00003","volume":"13","author":"R Brack-Werner","year":"1999","unstructured":"Brack-Werner R . Astrocytes: HIV cellular reservoirs and important participants in neuropathogenesis. AIDS 1999; 13: 1\u201322.","journal-title":"AIDS"},{"key":"BFcddis2016467_CR16","doi-asserted-by":"publisher","first-page":"317","DOI":"10.2353\/jmoldx.2008.070074","volume":"10","author":"JE Torres-Mu\u00f1oz","year":"2008","unstructured":"Torres-Mu\u00f1oz JE, N\u00fa\u00f1ez M, Petito CK . Successful application of hyperbranched multidisplacement genomic amplification to detect HIV-1 sequences in single neurons removed from autopsy brain sections by laser capture microdissection. J Mol Diagn 2008; 10: 317\u2013324.","journal-title":"J Mol Diagn"},{"key":"BFcddis2016467_CR17","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1385\/JMN:27:1:079","volume":"27","author":"C Cant\u00f3-Nogu\u00e9s","year":"2005","unstructured":"Cant\u00f3-Nogu\u00e9s C, S\u00e1nchez-Ram\u00f3n S, Alvarez S, Lacruz C, Mu\u00f1\u00f3z-Fern\u00e1ndez MA . HIV-1 infection of neurons might account for progressive HIV-1-associated encephalopathy in children. J Mol Neurosci 2005; 27: 79\u201389.","journal-title":"J Mol Neurosci"},{"key":"BFcddis2016467_CR18","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1128\/jvi.64.3.1383-1387.1990","volume":"64","author":"XL Li","year":"1990","unstructured":"Li XL, Moudgil T, Vinters HV, Ho DD . CD4-independent, productive infection of a neuronal cell line by human immunodeficiency virus type 1. J Virol 1990; 64: 1383\u20131387.","journal-title":"J Virol"},{"key":"BFcddis2016467_CR19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1742-6405-11-13","volume":"11","author":"VR Rao","year":"2014","unstructured":"Rao VR, Ruiz AP, Prasad VR . Viral and cellular factors underlying neuropathogenesis in HIV associated neurocognitive disorders (HAND). AIDS Res Ther 2014; 11: 13.","journal-title":"AIDS Res Ther"},{"key":"BFcddis2016467_CR20","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1046\/j.1365-2362.2002.01029.x","volume":"32","author":"M van de Bovenkamp","year":"2002","unstructured":"van de Bovenkamp M, Nottet HS, Pereira CF . Interactions of human immunodeficiency virus-1 proteins with neurons: possible role in the development of human immunodeficiency virus-1-associated dementia. Eur J Clin Invest 2002; 32: 619\u2013627.","journal-title":"Eur J Clin Invest"},{"key":"BFcddis2016467_CR21","doi-asserted-by":"crossref","first-page":"6094","DOI":"10.1128\/jvi.65.11.6094-6100.1991","volume":"65","author":"C Tornatore","year":"1991","unstructured":"Tornatore C, Nath A, Amemiya K, Major EO . Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta. J Virol 1991; 65: 6094\u20136100.","journal-title":"J Virol"},{"key":"BFcddis2016467_CR22","first-page":"659","volume":"144","author":"GJ Nuovo","year":"1994","unstructured":"Nuovo GJ, Gallery F, MacConnell P, Braun A . In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acids and tumor necrosis factor-alpha RNA in the central nervous system. Am J Pathol 1994; 144: 659\u2013666.","journal-title":"Am J Pathol"},{"key":"BFcddis2016467_CR23","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/embo-reports\/kve141","volume":"2","author":"M Geyer","year":"2001","unstructured":"Geyer M, Fackler OT, Peterlin BM . Structure--function relationships in HIV-1 Nef. EMBO Rep 2001; 2: 580\u2013585.","journal-title":"EMBO Rep"},{"key":"BFcddis2016467_CR24","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1097\/00002030-199509000-00004","volume":"9","author":"A Ranki","year":"1995","unstructured":"Ranki A, Nyberg M, Ovod V, Haltia M, Elovaara I, Raininko R et al. Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 1995; 9: 1001\u20131008.","journal-title":"AIDS"},{"key":"BFcddis2016467_CR25","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1089\/088922200750054684","volume":"16","author":"GA Robichaud","year":"2000","unstructured":"Robichaud GA, Poulin L . HIV type 1 nef gene inhibits tumor necrosis factor alpha-induced apoptosis and promotes cell proliferation through the action of MAPK and JNK in human glial cells. AIDS Res Hum Retroviruses 2000; 16: 1959\u20131965.","journal-title":"AIDS Res Hum Retroviruses"},{"key":"BFcddis2016467_CR26","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1111\/j.1600-0854.2009.01006.x","volume":"1","author":"M Lenassi","year":"2010","unstructured":"Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y et al. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic 2010; 1: 110\u2013122.","journal-title":"Traffic"},{"key":"BFcddis2016467_CR27","doi-asserted-by":"publisher","first-page":"5032","DOI":"10.1074\/jbc.M401202200","volume":"280","author":"R Madrid","year":"2005","unstructured":"Madrid R, Janvier K, Hitchin D, Day J, Coleman S, Noviello C et al. Nef-induced alteration of the early\/recycling endosomal compartment correlates with enhancement of HIV-1 infectivity. J Biol Chem 2005; 280: 5032\u20135044.","journal-title":"J Biol Chem"},{"key":"BFcddis2016467_CR28","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.virol.2004.08.024","volume":"329","author":"G Van Marle","year":"2004","unstructured":"Van Marle G, Henry S, Todoruk T, Sullivan A, Silva C, Rourke SB et al. Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10. Virology 2004; 329: 302\u2013318.","journal-title":"Virology"},{"key":"BFcddis2016467_CR29","first-page":"00164","volume":"S1359-6101","author":"ZA Percario","year":"2014","unstructured":"Percario ZA, Ali M, Mangino G, Affabris E . Nef, the shuttling molecular adaptor of HIV, influences the cytokine network. Cytokine Growth Factor Rev 2014piiS1359-6101: 00164\u201300166.","journal-title":"Cytokine Growth Factor Rev"},{"key":"BFcddis2016467_CR30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1742-4690-9-33","volume":"9","author":"J Mukerji","year":"2012","unstructured":"Mukerji J, Olivieri KC, Misra V, Agopian KA, Gabuzda D . Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation. Retrovirology 2012; 9: 33.","journal-title":"Retrovirology"},{"key":"BFcddis2016467_CR31","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0006-8993(00)02213-7","volume":"864","author":"G Trillo-Pazos","year":"2000","unstructured":"Trillo-Pazos G, McFarlane-Abdulla E, Campbell IC, Pilkington GJ, Everall IP . Recombinant nef HIV-IIIB protein is toxic to human neurons in culture. Brain Res 2000; 864: 315\u2013326.","journal-title":"Brain Res"},{"key":"BFcddis2016467_CR32","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1096\/fj.04-2308com","volume":"18","author":"E Mordelet","year":"2004","unstructured":"Mordelet E, Kissa K, Cressant A, Gray F, Ozden S, Vidal C et al. Histopathological and cognitive defects induced by Nef in the brain. FASEB J 2004; 18: 1851\u20131861.","journal-title":"FASEB J"},{"key":"BFcddis2016467_CR33","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.nbd.2012.08.007","volume":"49","author":"G Chompre","year":"2013","unstructured":"Chompre G, Cruz E, Maldonado L, Rivera-Amill V, Porter JT, Noel RJ Jr. . Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory. Neurobiol Dis 2013; 49: 128\u2013136.","journal-title":"Neurobiol Dis"},{"key":"BFcddis2016467_CR34","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/1742-4690-9-82","volume":"9","author":"H Koppensteiner","year":"2012","unstructured":"Koppensteiner H, Brack-Werner R, Schindler M . Macrophages and their relevance in human immunodeficiency virus type I infection. Retrovirology 2012; 9: 82.","journal-title":"Retrovirology"},{"key":"BFcddis2016467_CR35","doi-asserted-by":"publisher","first-page":"230","DOI":"10.3109\/13550281003735709","volume":"16","author":"SL Lamers","year":"2010","unstructured":"Lamers SL, Salemi M, Galligan DC, Morris A, Gray R, Fogel G et al. Human immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brain. J Neurovirol 2010; 16: 230\u2013241.","journal-title":"J Neurovirol"},{"issue":"Suppl 1","key":"BFcddis2016467_CR36","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1038\/sj.cdd.4401577","volume":"12","author":"MP Mattson","year":"2005","unstructured":"Mattson MP, Haughey NJ, Nath A . Cell death in HIV dementia. Cell Death Differ 2005; 12 ((Suppl 1)): 893\u2013904.","journal-title":"Cell Death Differ"},{"key":"BFcddis2016467_CR37","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s13365-014-0238-6","volume":"20","author":"GC Sampey","year":"2014","unstructured":"Sampey GC, Meyering SS, Asad Zadeh M, Saifuddin M, Hakami RM, Kashanchi F . Exosomes and their role in CNS viral infections. J Neurovirol 2014; 20: 199\u2013208.","journal-title":"J Neurovirol"},{"key":"BFcddis2016467_CR38","doi-asserted-by":"publisher","first-page":"e0124436","DOI":"10.1371\/journal.pone.0124436","volume":"10","author":"X Luo","year":"2015","unstructured":"Luo X, Fan Y, Park IW, He JJ . Exosomes are unlikely involved in intercellular nef transfer. PLoS One 2015; 10: e0124436.","journal-title":"PLoS One"},{"key":"BFcddis2016467_CR39","doi-asserted-by":"publisher","first-page":"2899","DOI":"10.1080\/15384101.2015.1069927","volume":"14","author":"AS Saribas","year":"2015","unstructured":"Saribas AS, Khalili K, Sariyer IK . Dysregulation of autophagy by HIV-1 Nef in human astrocytes. Cell Cycle 2015; 14: 2899\u20132904.","journal-title":"Cell Cycle"},{"key":"BFcddis2016467_CR40","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s12640-011-9279-2","volume":"21","author":"I Mocchetti","year":"2012","unstructured":"Mocchetti I, Bachis A, Avdoshina V . Neurotoxicity of human immunodeficiency virus-1: viral proteins and axonal transport. Neurotox Res 2012; 21: 79\u201389.","journal-title":"Neurotox Res"},{"key":"BFcddis2016467_CR41","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.mcn.2004.07.003","volume":"27","author":"BY Zhou","year":"2004","unstructured":"Zhou BY, Liu Y, Bo Kim, Xiao Y, He JJ . Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in astrocytes. Mol Cell Neurosci 2004; 27: 296\u2013305.","journal-title":"Mol Cell Neurosci"},{"key":"BFcddis2016467_CR42","doi-asserted-by":"publisher","first-page":"4387","DOI":"10.1007\/s00018-014-1702-4","volume":"22","author":"D Ferrell","year":"2014","unstructured":"Ferrell D, Giunta B . The impact of HIV-1 on neurogenesis: implications for HAND. Cell Mol Life Sci 2014; 22: 4387\u20134392.","journal-title":"Cell Mol Life Sci"},{"key":"BFcddis2016467_CR43","doi-asserted-by":"publisher","first-page":"43","DOI":"10.2174\/1570162X13666150311164201","volume":"13","author":"JA Fields","year":"2015","unstructured":"Fields JA, Dumaop W, Crews L, Adame A, Spencer B, Metcalf J et al. Mechanisms of HIV-1 Tat neurotoxicity via CDK5 translocation and hyper-activation: role in HIV-associated neurocognitive disorders. Curr HIV Res 2015; 13: 43\u201354.","journal-title":"Curr HIV Res"},{"key":"BFcddis2016467_CR44","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1523\/JNEUROSCI.3207-14.2015","volume":"35","author":"JA Fields","year":"2015","unstructured":"Fields JA, Dumaop W, Elueteri S, Campos S, Serger E, Trejo M et al. HIV-1 Tat alters neuronal autophagy by modulating autophagosome fusion to the lysosome: implications for HIV-associated neurocognitive disorders. J Neurosci 2015; 35: 1921\u20131938.","journal-title":"J Neurosci"},{"key":"BFcddis2016467_CR45","doi-asserted-by":"publisher","first-page":"e90620","DOI":"10.1371\/journal.pone.0090620","volume":"9","author":"LR Gray","year":"2014","unstructured":"Gray LR, Turville SG, Hitchen TL, Cheng WJ, Ellett AM, Salimi H et al. HIV-1 entry and trans-infection of astrocytes involves CD81 vesicles. PLoS One 2014; 9: e90620.","journal-title":"PLoS One"},{"key":"BFcddis2016467_CR46","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.ceb.2009.03.007","volume":"21","author":"M Simons","year":"2009","unstructured":"Simons M, Raposo G . Exosomes--vesicular carriers for intercellular communication. Curr Opin Cell Biol 2009; 21: 575\u2013581.","journal-title":"Curr Opin Cell Biol"},{"key":"BFcddis2016467_CR47","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1016\/j.bcp.2011.12.037","volume":"83","author":"S Pant","year":"2012","unstructured":"Pant S, Hilton H, Burczynski ME . The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacol 2012; 83: 1484\u20131494.","journal-title":"Biochem Pharmacol"},{"key":"BFcddis2016467_CR48","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.semcdb.2015.02.009","volume":"40","author":"DW Greening","year":"2015","unstructured":"Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W . Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 2015; 40: 72\u201381.","journal-title":"Semin Cell Dev Biol"},{"key":"BFcddis2016467_CR49","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3389\/fncel.2013.00182","volume":"7","author":"C Fr\u00fchbeis","year":"2013","unstructured":"Fr\u00fchbeis C, Fr\u00f6hlich D, Kuo WP, Kr\u00e4mer-Albers EM . Extracellular vesicles as mediators of neuron-glia communication. Front Cell Neurosci 2013; 7: 182.","journal-title":"Front Cell Neurosci"},{"key":"BFcddis2016467_CR50","doi-asserted-by":"publisher","first-page":"15482","DOI":"10.1523\/JNEUROSCI.3258-14.2014","volume":"34","author":"L Rajendran","year":"2014","unstructured":"Rajendran L, Bali J, Barr MM, Court FA, Kr\u00e4mer-Albers EM, Picou F et al. Emerging roles of extracellular vesicles in the nervous system. J Neurosci 2014; 34: 15482\u201315489.","journal-title":"J Neurosci"},{"key":"BFcddis2016467_CR51","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/1742-2094-11-68","volume":"11","author":"A Gupta","year":"2014","unstructured":"Gupta A, Pulliam L . Exosomes as mediators of neuroinflammation. J Neuroinflammation 2014; 11: 68.","journal-title":"J Neuroinflammation"},{"key":"BFcddis2016467_CR52","doi-asserted-by":"publisher","first-page":"11529","DOI":"10.1128\/JVI.01712-14","volume":"88","author":"C Arenaccio","year":"2014","unstructured":"Arenaccio C, Chiozzini C, Columba-Cabezas S, Manfredi F, Affabris E, Baur A 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. J Virol 2014; 88: 11529\u201311539.","journal-title":"J Virol"},{"key":"BFcddis2016467_CR53","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1089\/aid.2009.0068","volume":"26","author":"SA Ali","year":"2010","unstructured":"Ali SA, Huang MB, Campbell PE, Roth WW, Campbell T, Khan M et al. Genetic characterization of HIV type 1 Nef-induced vesicle secretion. AIDS Res Hum Retroviruses 2010; 26: 173\u2013192.","journal-title":"AIDS Res Hum Retroviruses"},{"key":"BFcddis2016467_CR54","doi-asserted-by":"publisher","first-page":"403","DOI":"10.3389\/fimmu.2014.00403","volume":"5","author":"F Baixauli","year":"2014","unstructured":"Baixauli F, L\u00f3pez-Ot\u00edn C, Mittelbrunn M . Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness. Front Immunol 2014; 5: 403.","journal-title":"Front Immunol"},{"key":"BFcddis2016467_CR55","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s00401-006-0037-0","volume":"111","author":"IC Anthony","year":"2006","unstructured":"Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE . Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy. Acta Neuropathol 2006; 111: 529\u2013538.","journal-title":"Acta Neuropathol"},{"key":"BFcddis2016467_CR56","doi-asserted-by":"crossref","unstructured":"Gisslen M, Krut J, Andreasson U, Blennow K, Cinque P, Brew BJ et al. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurol 2009; 9: 63.","DOI":"10.1186\/1471-2377-9-63"},{"issue":"7","key":"BFcddis2016467_CR57","doi-asserted-by":"publisher","first-page":"e68376","DOI":"10.1371\/journal.pone.0068376","volume":"8","author":"Carlos A. Barrero","year":"2013","unstructured":"Barrero CA, Datta PK, Sen S, Deshmane S, Amini S, Khalili K et al. HIV-1 Vpr modulates macrophage metabolic pathways: a SILAC-based quantitative analysis. PLoS One 2013; 8.","journal-title":"PLoS ONE"},{"key":"BFcddis2016467_CR58","unstructured":"Campbell TD, Khan M, Huang MB, Bond VC, Powell MD. HIV-1 Nef protein is secreted into vesicles that can fuse with target cells and virions. Ethn Dis 2008 18(2 Suppl 2): S2-14\u20139."},{"key":"BFcddis2016467_CR59","doi-asserted-by":"publisher","first-page":"24858","DOI":"10.3402\/jev.v3.24858","volume":"3","author":"J Van Deun","year":"2014","unstructured":"Van Deun J, Mestdagh P, Sormunen R, Cocquyt V, Vermaelen K, Vandesompele J et al. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J Extracell Vesicles 2014; 3: 24858.","journal-title":"J Extracell Vesicles"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis2016467.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016467","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016467.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T09:56:36Z","timestamp":1672653396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2016467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,12]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,1]]}},"alternative-id":["BFcddis2016467"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.467","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,12]]},"assertion":[{"value":"31 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}