{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:12:08Z","timestamp":1789996328480,"version":"4.0.1"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2004,4]]},"abstract":"\n Numerous host and viral factors likely participate in the onset and progression of HIV-1-associated dementia (HIVD). Previous studies have suggested that viral gene expression in resident central nervous system (CNS) cells of monocyte\/macrophage lineage play a central role in the production of neurotoxic viral proteins and infectious virus, deregulation of cellular gene expression, and\/or dysfunction of glial and neuronal cell populations. HIV-1 replication is regulated, in part, by interactions between cellular transcription factors and the viral\n trans-<\/jats:italic>\n activators, Tat and viral protein R (Vpr), with\n cis<\/jats:italic>\n -acting promoter elements within the LTR. We have previously demonstrated that Vpr binds with high affinity to selected sequence configurations within CCAAT\/enhancer binding protein (C\/EBP) site I and downstream sequences immediately adjacent to this site. Studies reported herein establish a correlation between the diagnosis of HIVD and the increased prevalence of HIV-1 LTRs containing a C\/EBP binding site I that exhibits high affinity for Vpr. To this end, the interaction of Vpr with C\/EBP site I variants in 47 LTRs from three nondemented patients and 96 LTRs from seven demented patients was examined. Competition electrophoretic mobility shift (EMS) analyses were utilized to examine Vpr binding to oligonucleotide probes containing C\/EBP site I variants. We demonstrated that 89% of LTRs derived from patients exhibiting clinical dementia contained C\/EBP site I configurations that displayed a high relative affinity for Vpr, while only 11% of LTRs contained C\/EBP site I configurations that exhibited a low relative affinity Vpr binding phenotype. In contrast, examination of LTRs derived from patients lacking clinically evident dementia revealed that only 53% of brain-derived LTRs contained C\/EBP site I configurations that displayed a high relative affinity for Vpr, while 47% of LTRs contained C\/EBP site I configurations that exhibited a low relative affinity Vpr binding phenotype. We propose that sequence-specific interactions between\n cis<\/jats:italic>\n -acting elements in the LTR, members of the C\/EBP family of transcription factors, and the virion-associated\n trans<\/jats:italic>\n -activator protein Vpr play important roles in the pathogenesis of HIVD.\n <\/jats:p>","DOI":"10.1089\/104454904773819842","type":"journal-article","created":{"date-parts":[[2004,4,27]],"date-time":"2004-04-27T22:07:38Z","timestamp":1083103658000},"page":"261-269","source":"Crossref","is-referenced-by-count":31,"title":["High-Affinity Interaction between HIV-1 Vpr and Specific Sequences That Span the C\/EBP and Adjacent NF-\n \u03ba<\/i>\n B Sites within the HIV-1 LTR Correlate with HIV-1-Associated Dementia"],"prefix":"10.1177","volume":"23","author":[{"given":"Tricia H.","family":"Burdo","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nonnemacher","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan P.","family":"Irish","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine H.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred C.","family":"Krebs","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Gartner","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Wigdahl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2004,4,1]]},"container-title":["DNA and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/104454904773819842","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/104454904773819842","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T15:12:41Z","timestamp":1773241961000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/104454904773819842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1089\/104454904773819842"],"URL":"https:\/\/doi.org\/10.1089\/104454904773819842","relation":{},"ISSN":["1044-5498","1557-7430"],"issn-type":[{"value":"1044-5498","type":"print"},{"value":"1557-7430","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4]]}}}