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In the present study, we examine the need for intracellular cholesterol trafficking pathways with respect to HIV-1 biogenesis using Niemann-Pick type C-1 (NPC1)-deficient (NPCD) cells, wherein these pathways are severely compromised, causing massive accumulation of cholesterol in late endosomal\/lysosomal (LE\/L) compartments. We have found that induction of an NPC disease-like phenotype through treatment of various cell types with the commonly used hydrophobic amine drug U18666A resulted in profound suppression of HIV-1 release. Further, NPCD Epstein-Barr virus-transformed B lymphocytes and fibroblasts from patients with NPC disease infected with a CD4-independent strain of HIV-1 or transfected with an HIV-1 proviral clone, respectively, replicated HIV-1 poorly compared to normal cells. Infection of the NPCD fibroblasts with a vesicular stomatitis virus G-pseudotyped strain of HIV-1 produced similar results, suggesting a postentry block to HIV-1 replication in these cells. Examination of these cells using confocal microscopy showed an accumulation and stabilization of Gag in LE\/L compartments. Additionally, normal HIV-1 production could be restored in NPCD cells upon expression of a functional NPC1 protein, and overexpression of NPC1 increased HIV-1 release. Taken together, our findings demonstrate that intact intracellular cholesterol trafficking pathways mediated by NPC1 are needed for efficient HIV-1 production.<\/jats:p>","DOI":"10.1128\/jvi.00259-09","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T00:51:20Z","timestamp":1243471880000},"page":"7982-7995","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":72,"title":["Deficiency of Niemann-Pick Type C-1 Protein Impairs Release of Human Immunodeficiency Virus Type 1 and Results in Gag Accumulation in Late Endosomal\/Lysosomal Compartments"],"prefix":"10.1128","volume":"83","author":[{"given":"Yuyang","family":"Tang","sequence":"first","affiliation":[{"name":"Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, Tennessee 37208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihid Carneiro","family":"Leao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebony M.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, Tennessee 37208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin Shepard","family":"Broughton","sequence":"additional","affiliation":[{"name":"Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, Tennessee 37208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E. 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