{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:44:24Z","timestamp":1793285064290,"version":"4.5.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["1R21DA051813"],"award-info":[{"award-number":["1R21DA051813"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R21 DA050176"],"award-info":[{"award-number":["R21 DA050176"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["RO1 N5099029"],"award-info":[{"award-number":["RO1 N5099029"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Retrovirology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Extracellular Vesicles (EV) recently have been implicated in the pathogenesis of HIV-1 syndromes, including neuroinflammation and HIV-1 associated neurological disorder (HAND). Cocaine, an illicit stimulant drug used worldwide is known to exacerbate these HIV-1 associated neurological syndromes. However, the effects of cocaine on EV biogenesis and roles of EVs in enhancing HIV-1 pathogenesis are not yet well defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we investigated the effects of cocaine on EV biogenesis and release in HIV-1 infected immune cells and explored their roles in elicitation of neuroinflammation. We found that cocaine significantly augmented the release of EVs from uninfected and HIV-1 infected T-cells, DCs and macrophages. Further analysis of the molecular components of EVs revealed enhanced expression of adhesion molecules integrin \u03b21 and LFA-1 in those EVs derived from cocaine treated cells. Intriguingly, in EVs derived from HIV-1 infected cells, cocaine treatment significantly increased the levels of viral genes in EVs released from macrophages and DCs, but not in T-cells. Exploring the molecular mechanism to account for this, we found that DCs and macrophages showed enhanced expression of the cocaine receptor Sigma 1-Receptor compared to T-cells. In addition, we found that cocaine significantly altered the integrity of the RNA-induced silencing complex (RISC) in HIV-1 infected macrophages and DCs compared to untreated HIV-1 infected cells. Characterizing further the molecular mechanisms involved in how cocaine increased EV release, we found that cocaine decreased the expression of the interferon-inducible protein BST-2; this resulted in altered trafficking of intracellular virus containing vesicles and EV biogenesis and release. We also observed EVs released from cocaine treated HIV-1 infected macrophages and DCs enhanced HIV-1 trans-infection to T-cells compared to those from untreated and HIV-1 infected cells. These EVs triggered release of proinflammatory cytokines in human brain microvascular endothelial cells (HBMECs) and altered monolayer integrity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, our results provide a novel mechanism which helps to elucidate the enhanced prevalence of neurological disorders in cocaine using HIV-1 infected individuals and offers insights into developing novel therapeutic strategies against HAND in these hosts.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12977-021-00570-4","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T10:03:27Z","timestamp":1631786607000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cocaine augments neuro-inflammation via modulating extracellular vesicle release in HIV-1 infected immune cells"],"prefix":"10.1186","volume":"18","author":[{"given":"Manojkumar","family":"Narayanan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutuja","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatah","family":"Kashanchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"570_CR1","doi-asserted-by":"publisher","first-page":"451","DOI":"10.15698\/mic2016.09.529","volume":"3","author":"JC Becerra","year":"2016","unstructured":"Becerra JC, Bildstein LS, Gach JS. Recent insights into the HIV\/AIDS pandemic. Microb Cell. 2016;3:451\u201375. https:\/\/doi.org\/10.15698\/mic2016.09.529.","journal-title":"Microb Cell"},{"key":"570_CR2","doi-asserted-by":"publisher","first-page":"390","DOI":"10.3389\/fmicb.2017.00390","volume":"8","author":"S Harada","year":"2017","unstructured":"Harada S, Yoshimura K. Driving HIV-1 into a vulnerable corner by taking advantage of viral adaptation and evolution. Front Microbiol. 2017;8:390. https:\/\/doi.org\/10.3389\/fmicb.2017.00390.","journal-title":"Front Microbiol"},{"key":"570_CR3","doi-asserted-by":"publisher","first-page":"412","DOI":"10.2174\/1570162X14666160324125158","volume":"14","author":"Y Cai","year":"2016","unstructured":"Cai Y, Yang L, Callen S, Buch S. Multiple faceted roles of cocaine in potentiation of HAND. Curr HIV Res. 2016;14:412\u20136.","journal-title":"Curr HIV Res"},{"key":"570_CR4","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1007\/s12640-012-9334-7","volume":"23","author":"KH Clark","year":"2013","unstructured":"Clark KH, Wiley CA, Bradberry CW. Psychostimulant abuse and neuroinflammation: emerging evidence of their interconnection. Neurotox Res. 2013;23:174\u201388. https:\/\/doi.org\/10.1007\/s12640-012-9334-7.","journal-title":"Neurotox Res"},{"key":"570_CR5","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1002\/hup.1251","volume":"27","author":"HC Fox","year":"2012","unstructured":"Fox HC, et al. Immune system inflammation in cocaine dependent individuals: implications for medications development. Hum Psychopharmacol. 2012;27:156\u201366. https:\/\/doi.org\/10.1002\/hup.1251.","journal-title":"Hum Psychopharmacol"},{"key":"570_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbi.2014.10.008","volume":"45","author":"S Hong","year":"2015","unstructured":"Hong S, Banks WA. Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications. Brain Behav Immun. 2015;45:1\u201312. https:\/\/doi.org\/10.1016\/j.bbi.2014.10.008.","journal-title":"Brain Behav Immun"},{"key":"570_CR7","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1189\/jlb.4A0714-356R","volume":"97","author":"AB Addai","year":"2015","unstructured":"Addai AB, et al. Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients. J Leukoc Biol. 2015;97:779\u201390. https:\/\/doi.org\/10.1189\/jlb.4A0714-356R.","journal-title":"J Leukoc Biol"},{"key":"570_CR8","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1093\/oxfordjournals.aje.a116021","volume":"134","author":"JC Anthony","year":"1991","unstructured":"Anthony JC, et al. New evidence on intravenous cocaine use and the risk of infection with human immunodeficiency virus type 1. Am J Epidemiol. 1991;134:1175\u201389.","journal-title":"Am J Epidemiol"},{"key":"570_CR9","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.3389\/fmicb.2015.01111","volume":"6","author":"S Dash","year":"2015","unstructured":"Dash S, Balasubramaniam M, Villalta F, Dash C, Pandhare J. Impact of cocaine abuse on HIV pathogenesis. Front Microbiol. 2015;6:1111. https:\/\/doi.org\/10.3389\/fmicb.2015.01111.","journal-title":"Front Microbiol"},{"key":"570_CR10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jneuroim.2003.10.007","volume":"147","author":"JH Khalsa","year":"2004","unstructured":"Khalsa JH, Royal W. Do drugs of abuse impact on HIV disease? J Neuroimmunol. 2004;147:6\u20138.","journal-title":"J Neuroimmunol"},{"key":"570_CR11","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1189\/jlb.1112566","volume":"94","author":"SG Kim","year":"2013","unstructured":"Kim SG, et al. Cocaine exposure enhances permissiveness of quiescent T cells to HIV infection. J Leukoc Biol. 2013;94:835\u201343. https:\/\/doi.org\/10.1189\/jlb.1112566.","journal-title":"J Leukoc Biol"},{"key":"570_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051387","volume":"7","author":"CK Mantri","year":"2012","unstructured":"Mantri CK, Pandhare Dash J, Mantri JV, Dash CC. Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. PLoS ONE. 2012;7: e51387. https:\/\/doi.org\/10.1371\/journal.pone.0051387.","journal-title":"PLoS ONE"},{"key":"570_CR13","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1128\/CDLI.7.1.96-100.2000","volume":"7","author":"MP Nair","year":"2000","unstructured":"Nair MP, et al. Cocaine differentially modulates chemokine production by mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients. Clin Diagn Lab Immunol. 2000;7:96\u2013100.","journal-title":"Clin Diagn Lab Immunol"},{"key":"570_CR14","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/0-306-47611-8_28","volume":"493","author":"MP Nair","year":"2001","unstructured":"Nair MP, et al. Effect of cocaine on chemokine and CCR-5 gene expression by mononuclear cells from normal donors and HIV-1 infected patients. Adv Exp Med Biol. 2001;493:235\u201340. https:\/\/doi.org\/10.1007\/0-306-47611-8_28.","journal-title":"Adv Exp Med Biol"},{"key":"570_CR15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083682","volume":"8","author":"J Napuri","year":"2013","unstructured":"Napuri J, et al. Cocaine enhances HIV-1 infectivity in monocyte derived dendritic cells by suppressing microRNA-155. PLoS ONE. 2013;8: e83682. https:\/\/doi.org\/10.1371\/journal.pone.0083682.","journal-title":"PLoS ONE"},{"key":"570_CR16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4049\/jimmunol.146.1.81","volume":"146","author":"PK Peterson","year":"1991","unstructured":"Peterson PK, et al. Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell cocultures. Involvement of transforming growth factor-beta. J Immunol. 1991;146:81\u20134.","journal-title":"J Immunol"},{"key":"570_CR17","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.brainres.2006.09.034","volume":"1123","author":"JL Reynolds","year":"2006","unstructured":"Reynolds JL, et al. Proteomic analysis of the effects of cocaine on the enhancement of HIV-1 replication in normal human astrocytes (NHA). Brain Res. 2006;1123:226\u201336. https:\/\/doi.org\/10.1016\/j.brainres.2006.09.034.","journal-title":"Brain Res"},{"key":"570_CR18","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1086\/339012","volume":"185","author":"MD Roth","year":"2002","unstructured":"Roth MD, et al. Cocaine enhances human immunodeficiency virus replication in a model of severe combined immunodeficient mice implanted with human peripheral blood leukocytes. J Infect Dis. 2002;185:701\u20135. https:\/\/doi.org\/10.1086\/339012.","journal-title":"J Infect Dis"},{"key":"570_CR19","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1189\/jlb.0405219","volume":"78","author":"MD Roth","year":"2005","unstructured":"Roth MD, Whittaker KM, Choi R, Tashkin DP, Baldwin GC. Cocaine and sigma-1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model. J Leukoc Biol. 2005;78:1198\u2013203. https:\/\/doi.org\/10.1189\/jlb.0405219.","journal-title":"J Leukoc Biol"},{"key":"570_CR20","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3109\/13550289809114228","volume":"4","author":"L Zhang","year":"1998","unstructured":"Zhang L, et al. Cocaine opens the blood-brain barrier to HIV-1 invasion. J Neurovirol. 1998;4:619\u201326.","journal-title":"J Neurovirol"},{"key":"570_CR21","doi-asserted-by":"publisher","first-page":"40648","DOI":"10.1038\/srep40648","volume":"7","author":"A Prasad","year":"2017","unstructured":"Prasad A, Kulkarni R, Jiang S, Groopman JE. Cocaine enhances DC to T-cell HIV-1 transmission by activating DC-SIGN\/LARG\/LSP1 complex and facilitating infectious synapse formation. Sci Rep. 2017;7:40648. https:\/\/doi.org\/10.1038\/srep40648.","journal-title":"Sci Rep"},{"key":"570_CR22","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s12031-014-0365-9","volume":"55","author":"C Carone","year":"2015","unstructured":"Carone C, et al. In vitro effects of cocaine on tunneling nanotube formation and extracellular vesicle release in glioblastoma cell cultures. J Mol Neurosci. 2015;55:42\u201350. https:\/\/doi.org\/10.1007\/s12031-014-0365-9.","journal-title":"J Mol Neurosci"},{"key":"570_CR23","doi-asserted-by":"publisher","first-page":"3204","DOI":"10.3390\/v7062770","volume":"7","author":"HS Chahar","year":"2015","unstructured":"Chahar HS, Bao X, Casola A. Exosomes and their role in the life cycle and pathogenesis of RNA viruses. Viruses. 2015;7:3204\u201325. https:\/\/doi.org\/10.3390\/v7062770.","journal-title":"Viruses"},{"key":"570_CR24","doi-asserted-by":"publisher","first-page":"744","DOI":"10.4049\/jimmunol.1102244","volume":"189","author":"I Kadiu","year":"2012","unstructured":"Kadiu I, Narayanasamy P, Dash PK, Zhang W, Gendelman HE. Biochemical and biologic characterization of exosomes and microvesicles as facilitators of HIV-1 infection in macrophages. J Immunol. 2012;189:744\u201354. https:\/\/doi.org\/10.4049\/jimmunol.1102244.","journal-title":"J Immunol"},{"key":"570_CR25","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1073\/pnas.0507995103","volume":"103","author":"RD Wiley","year":"2006","unstructured":"Wiley RD, Gummuluru S. Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proc Natl Acad Sci U S A. 2006;103:738\u201343. https:\/\/doi.org\/10.1073\/pnas.0507995103.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"570_CR26","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. https:\/\/doi.org\/10.1186\/1742-2094-11-68.","journal-title":"J Neuroinflammation"},{"key":"570_CR27","doi-asserted-by":"publisher","first-page":"400","DOI":"10.2174\/1570162X14666160324124558","volume":"14","author":"S Malik","year":"2016","unstructured":"Malik S, Eugenin EA. Mechanisms of HIV neuropathogenesis: role of cellular communication systems. Curr HIV Res. 2016;14:400\u201311.","journal-title":"Curr HIV Res"},{"key":"570_CR28","doi-asserted-by":"publisher","first-page":"6206","DOI":"10.2174\/1381612823666170913164738","volume":"23","author":"J Matsumoto","year":"2017","unstructured":"Matsumoto J, Stewart T, Banks WA, Zhang J. The transport mechanism of extracellular vesicles at the blood-brain barrier. Curr Pharm Des. 2017;23:6206\u201314. https:\/\/doi.org\/10.2174\/1381612823666170913164738.","journal-title":"Curr Pharm Des"},{"key":"570_CR29","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12987-018-0104-7","volume":"15","author":"SH Ramirez","year":"2018","unstructured":"Ramirez SH, Andrews AM, Paul D, Pachter JS. Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers. Fluids Barriers CNS. 2018;15:19. https:\/\/doi.org\/10.1186\/s12987-018-0104-7.","journal-title":"Fluids Barriers CNS"},{"key":"570_CR30","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s13365-014-0238-6","volume":"20","author":"GC Sampey","year":"2014","unstructured":"Sampey GC, et al. Exosomes and their role in CNS viral infections. J Neurovirol. 2014;20:199\u2013208. https:\/\/doi.org\/10.1007\/s13365-014-0238-6.","journal-title":"J Neurovirol"},{"key":"570_CR31","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.chom.2012.07.011","volume":"12","author":"H Chu","year":"2012","unstructured":"Chu H, et al. Tetherin\/BST-2 is essential for the formation of the intracellular virus-containing compartment in HIV-infected macrophages. Cell Host Microbe. 2012;12:360\u201372. https:\/\/doi.org\/10.1016\/j.chom.2012.07.011.","journal-title":"Cell Host Microbe"},{"key":"570_CR32","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1128\/jvi.64.2.621-629.1990","volume":"64","author":"T Klimkait","year":"1990","unstructured":"Klimkait T, Strebel K, Hoggan MD, Martin MA, Orenstein JM. The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol. 1990;64:621\u20139.","journal-title":"J Virol"},{"key":"570_CR33","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/nature06553","volume":"451","author":"SJ Neil","year":"2008","unstructured":"Neil SJ, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature. 2008;451:425\u201330. https:\/\/doi.org\/10.1038\/nature06553.","journal-title":"Nature"},{"key":"570_CR34","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.chom.2008.03.001","volume":"3","author":"N Van Damme","year":"2008","unstructured":"Van Damme N, et al. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe. 2008;3:245\u201352. https:\/\/doi.org\/10.1016\/j.chom.2008.03.001.","journal-title":"Cell Host Microbe"},{"key":"570_CR35","doi-asserted-by":"publisher","first-page":"321","DOI":"10.2174\/157016212800792522","volume":"10","author":"H Fujita","year":"2012","unstructured":"Fujita H, Fujimoto K, Tokunaga K, Tanaka Y. Intracellular logistics of BST-2\/tetherin. Curr HIV Res. 2012;10:321\u20136.","journal-title":"Curr HIV Res"},{"key":"570_CR36","doi-asserted-by":"publisher","first-page":"235","DOI":"10.2174\/1570162X14999160224102752","volume":"14","author":"SX Li","year":"2016","unstructured":"Li SX, Barrett BS, Guo K, Santiago ML. Tetherin\/BST-2: restriction factor or immunomodulator? Curr HIV Res. 2016;14:235\u201346.","journal-title":"Curr HIV Res"},{"key":"570_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001265","volume":"7","author":"K Janvier","year":"2011","unstructured":"Janvier K, et al. The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2\/tetherin down-regulation. PLoS Pathog. 2011;7: e1001265. https:\/\/doi.org\/10.1371\/journal.ppat.1001265.","journal-title":"PLoS Pathog"},{"key":"570_CR38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002609","volume":"8","author":"T Kueck","year":"2012","unstructured":"Kueck T, Neil SJ. A cytoplasmic tail determinant in HIV-1 Vpu mediates targeting of tetherin for endosomal degradation and counteracts interferon-induced restriction. PLoS Pathog. 2012;8: e1002609. https:\/\/doi.org\/10.1371\/journal.ppat.1002609.","journal-title":"PLoS Pathog"},{"key":"570_CR39","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17180","author":"JR Edgar","year":"2016","unstructured":"Edgar JR, Manna PT, Nishimura S, Banting G, Robinson MS. Tetherin is an exosomal tether. Elife. 2016. https:\/\/doi.org\/10.7554\/eLife.17180.","journal-title":"Elife"},{"key":"570_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.60","author":"N Raab-Traub","year":"2017","unstructured":"Raab-Traub N, Dittmer DP. Viral effects on the content and function of extracellular vesicles. Nat Rev Microbiol. 2017. https:\/\/doi.org\/10.1038\/nrmicro.2017.60.","journal-title":"Nat Rev Microbiol"},{"key":"570_CR41","doi-asserted-by":"publisher","first-page":"14787","DOI":"10.1038\/s41598-017-14817-8","volume":"7","author":"R Kulkarni","year":"2017","unstructured":"Kulkarni R, Prasad A. Exosomes derived from HIV-1 infected DCs mediate viral trans-infection via fibronectin and galectin-3. Sci Rep. 2017;7:14787. https:\/\/doi.org\/10.1038\/s41598-017-14817-8.","journal-title":"Sci Rep"},{"key":"570_CR42","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1007\/s11481-011-9298-z","volume":"6","author":"I Kadiu","year":"2011","unstructured":"Kadiu I, Gendelman HE. Human immunodeficiency virus type 1 endocytic trafficking through macrophage bridging conduits facilitates spread of infection. J Neuroimmune Pharmacol. 2011;6:658\u201375. https:\/\/doi.org\/10.1007\/s11481-011-9298-z.","journal-title":"J Neuroimmune Pharmacol"},{"key":"570_CR43","doi-asserted-by":"publisher","first-page":"40884","DOI":"10.1074\/jbc.R112.415448","volume":"287","author":"Z Klase","year":"2012","unstructured":"Klase Z, Houzet L, Jeang KT. MicroRNAs and HIV-1: complex interactions. J Biol Chem. 2012;287:40884\u201390. https:\/\/doi.org\/10.1074\/jbc.R112.415448.","journal-title":"J Biol Chem"},{"key":"570_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2021.01.007","author":"J Makarova","year":"2021","unstructured":"Makarova J, Turchinovich A, Shkurnikov M, Tonevitsky A. Extracellular miRNAs and cell-cell communication: problems and prospects. Trends Biochem Sci. 2021. https:\/\/doi.org\/10.1016\/j.tibs.2021.01.007.","journal-title":"Trends Biochem Sci"},{"key":"570_CR45","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/1873-3468.13788","volume":"594","author":"R Kulkarni","year":"2020","unstructured":"Kulkarni R, Jiang S, Birrane G, Prasad A. Lymphocyte-specific protein 1 (LSP1) regulates bone marrow stromal cell antigen 2 (BST-2)-mediated intracellular trafficking of HIV-1 in dendritic cells. FEBS Lett. 2020;594:1947\u201359. https:\/\/doi.org\/10.1002\/1873-3468.13788.","journal-title":"FEBS Lett"},{"key":"570_CR46","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15432","author":"D Perocheau","year":"2021","unstructured":"Perocheau D, Touramanidou L, Gurung S, Gissen P, Baruteau J. Clinical applications for exosomes: are we there yet? Br J Pharmacol. 2021. https:\/\/doi.org\/10.1111\/bph.15432.","journal-title":"Br J Pharmacol"},{"key":"570_CR47","doi-asserted-by":"publisher","first-page":"3624","DOI":"10.1128\/jvi.77.6.3624-3633.2003","volume":"77","author":"JJ von Lindern","year":"2003","unstructured":"von Lindern JJ, et al. Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages. J Virol. 2003;77:3624\u201333. https:\/\/doi.org\/10.1128\/jvi.77.6.3624-3633.2003.","journal-title":"J Virol"},{"key":"570_CR48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47209","author":"Y Nakamura","year":"2019","unstructured":"Nakamura Y, et al. Cocaine-induced endocannabinoid signaling mediated by sigma-1 receptors and extracellular vesicle secretion. Elife. 2019. https:\/\/doi.org\/10.7554\/eLife.47209.","journal-title":"Elife"},{"key":"570_CR49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0132127","volume":"10","author":"V Vongrad","year":"2015","unstructured":"Vongrad V, et al. HIV-1 RNAs are not part of the argonaute 2 associated RNA interference pathway in macrophages. PLoS ONE. 2015;10: e0132127. https:\/\/doi.org\/10.1371\/journal.pone.0132127.","journal-title":"PLoS ONE"},{"key":"570_CR50","doi-asserted-by":"publisher","first-page":"10592","DOI":"10.1073\/pnas.1831413100","volume":"100","author":"SJ Gould","year":"2003","unstructured":"Gould SJ, Booth AM, Hildreth JE. The Trojan exosome hypothesis. Proc Natl Acad Sci U S A. 2003;100:10592\u20137. https:\/\/doi.org\/10.1073\/pnas.1831413100.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"570_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000740","volume":"6","author":"N Izquierdo-Useros","year":"2010","unstructured":"Izquierdo-Useros N, et al. HIV and mature dendritic cells: Trojan exosomes riding the Trojan horse? PLoS Pathog. 2010;6: e1000740. https:\/\/doi.org\/10.1371\/journal.ppat.1000740.","journal-title":"PLoS Pathog"},{"key":"570_CR52","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.3390\/v7072810","volume":"7","author":"MN Madison","year":"2015","unstructured":"Madison MN, Okeoma CM. Exosomes: implications in HIV-1 pathogenesis. Viruses. 2015;7:4093\u2013118. https:\/\/doi.org\/10.3390\/v7072810.","journal-title":"Viruses"},{"key":"570_CR53","doi-asserted-by":"publisher","first-page":"20014","DOI":"10.1074\/jbc.M112.438895","volume":"288","author":"A Narayanan","year":"2013","unstructured":"Narayanan A, et al. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. J Biol Chem. 2013;288:20014\u201333. https:\/\/doi.org\/10.1074\/jbc.M112.438895.","journal-title":"J Biol Chem"}],"container-title":["Retrovirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12977-021-00570-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12977-021-00570-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12977-021-00570-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T11:07:15Z","timestamp":1673262435000},"score":1,"resource":{"primary":{"URL":"https:\/\/retrovirology.biomedcentral.com\/articles\/10.1186\/s12977-021-00570-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,16]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["570"],"URL":"https:\/\/doi.org\/10.1186\/s12977-021-00570-4","relation":{},"ISSN":["1742-4690"],"issn-type":[{"value":"1742-4690","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,16]]},"assertion":[{"value":"6 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Buffy coats were obtained in compliance with the Beth Israel Deaconess Medical Center Committee on Clinical Investigations (CCI) protocol #2008-P-000418\/5. Buffy coats were provided at this institution for research purposes; therefore, no informed consent was further needed. In addition, buffy coats were provided without identifiers. This study was approved by Beth Israel Deaconess Medical Center\u2019s CCI, Institutional Review Board, and Privacy Board appointed to review research involving human subjects. The experimental procedures were carried out in strict accordance with approved guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26"}}