{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:29:21Z","timestamp":1773865761477,"version":"3.50.1"},"reference-count":97,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"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":["R21DA046855, R01DA042379"],"award-info":[{"award-number":["R21DA046855, R01DA042379"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Despite the success of combinational antiretroviral therapy (cART), the high pervasiveness of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) poses a significant challenge for society. Methamphetamine (meth) and related amphetamine compounds, which are potent psychostimulants, are among the most commonly used illicit drugs. Intriguingly, HIV-infected individuals who are meth users have a comparatively higher rate of neuropsychological impairment and exhibit a higher viral load in the brain than infected individuals who do not abuse meth. Effectively, all cell types secrete nano-sized lipid membrane vesicles, referred to as extracellular vesicles (EVs) that can function as intercellular communication to modulate the physiology and pathology of the cells. This study shows that meth treatments on chronically HIV-infected promonocytic U1 cells induce the release of EVs that promote cellular clustering and syncytia formation, a phenomenon that facilitates HIV pathogenesis. Our analysis also revealed that meth exposure increased intercellular adhesion molecule-1 (ICAM-1) and HIV-Nef protein expression in both large (10 K) and small (100 K) EVs. Further, when meth EVs are applied to uninfected na\u00efve monocyte-derived macrophages (MDMs), we saw a significant increase in cell clustering and syncytia formation. Furthermore, treatment of MDMs with antibodies against ICAM-1 and its receptor, lymphocyte function-associated antigen 1 (LFA1), substantially blocked syncytia formation, and consequently reduced the number of multinucleated cells. In summary, our findings reveal that meth exacerbates HIV pathogenesis in the brain through release of proadhesive EVs, promoting syncytia formation and thereby aiding in the progression of HIV infection in uninfected cells.<\/jats:p>","DOI":"10.3390\/v14030550","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T01:50:53Z","timestamp":1646790653000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Methamphetamine Induces the Release of Proadhesive Extracellular Vesicles and Promotes Syncytia Formation: A Potential Role in HIV-1 Neuropathogenesis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-2743","authenticated-orcid":false,"given":"Subhash","family":"Chand","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"DeMarino","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austin","family":"Gowen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Cowen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Al-Sharif","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"},{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9681-2780","authenticated-orcid":false,"given":"Fatah","family":"Kashanchi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1530-0527","authenticated-orcid":false,"given":"Sowmya V.","family":"Yelamanchili","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1212\/WNL.0000000000002277","article-title":"Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study","volume":"86","author":"Sacktor","year":"2015","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s11065-009-9102-5","article-title":"Cognitive Neuropsychology of HIV-Associated Neurocognitive Disorders","volume":"19","author":"Woods","year":"2009","journal-title":"Neuropsychol. 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