{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:46:36Z","timestamp":1791215196706,"version":"4.1.0"},"reference-count":54,"publisher":"Society for Neuroscience","issue":"14","license":[{"start":{"date-parts":[[2007,10,4]],"date-time":"2007-10-04T00:00:00Z","timestamp":1191456000000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,4,4]]},"abstract":"<jats:p>Despite the introduction of highly active antiretroviral therapy, dementia caused by human immunodeficiency virus-1 (HIV-1) infection remains a devastating and common neurological disorder. Although the mechanisms governing neurodegeneration during HIV-1 infection remain uncertain, the HIV-1 accessory protein, viral protein R (Vpr), has been proposed as a neurotoxic protein. Herein, we report that Vpr protein and transcript were present in the brains of HIV-infected persons. Moreover, soluble Vpr caused neuronal apoptosis, involving cytochrome<jats:italic>c<\/jats:italic>extravasation, p53 induction, and activation of caspase-9 while exerting a depressive effect on whole-cell currents in neurons (<jats:italic>p<\/jats:italic>&lt; 0.05), which was inhibited by iberiotoxin. Vpr-activated glial cells secreted neurotoxins in a concentration-dependent manner (<jats:italic>p<\/jats:italic>&lt; 0.001). Transgenic (Tg) mice expressing Vpr in brain monocytoid cells displayed the transgene principally in the basal ganglia (<jats:italic>p<\/jats:italic>&lt; 0.05) and cerebral cortex (<jats:italic>p<\/jats:italic>&lt; 0.01) compared with hindbrain expression. Vpr was released from cultured transgenic macrophages, which was cytotoxic to neurons and was blocked by anti-Vpr antibody (<jats:italic>p<\/jats:italic>&lt; 0.05). Neuronal injury was observed in Tg animals compared with wild-type littermates, chiefly affecting GAD65 (<jats:italic>p<\/jats:italic>&lt; 0.01) and vesicular acetylcholine transferase (<jats:italic>p<\/jats:italic>&lt; 0.001) immunopositive neuronal populations in the basal ganglia. There was also a loss of subcortical synaptophysin (<jats:italic>p<\/jats:italic>&lt; 0.001) immunoreactivity as well as an increase in activated caspase-3, which was accompanied by a hyperexcitable neurobehavioral phenotype (<jats:italic>p<\/jats:italic>&lt; 0.05). Thus, HIV-1 Vpr caused neuronal death through convergent pathogenic mechanisms with ensuing<jats:italic>in vivo<\/jats:italic>neurodegeneration, yielding new insights into the mechanisms by which HIV-1 injures the nervous system.<\/jats:p>","DOI":"10.1523\/jneurosci.5522-06.2007","type":"journal-article","created":{"date-parts":[[2007,4,4]],"date-time":"2007-04-04T17:02:44Z","timestamp":1175706164000},"page":"3703-3711","source":"Crossref","is-referenced-by-count":123,"title":["HIV-1 Vpr Causes Neuronal Apoptosis and<i>In Vivo<\/i>Neurodegeneration"],"prefix":"10.1523","volume":"27","author":[{"given":"Gareth J.","family":"Jones","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola L.","family":"Barsby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9ric 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