HIV gene expression from intact proviruses positioned in bacterial artificial chromosomes at integration sites previously identified in latently infected T cells
- Department of Cell Biology, University of Alabama at Birmingham, 802 Kaul Building, 720 20th Street South, Birmingham, AL 35294 (United States)
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)
HIV integration predominantly occurs in introns of transcriptionally active genes. To study the impact of the integration site on HIV gene expression, a complete HIV-1 provirus (with GFP as a fusion with Nef) was inserted into bacterial artificial chromosomes (BACs) at three sites previously identified in latent T cells of patients: topoisomerase II (Top2A), DNA methyltransferase 1 (DNMT1), or basic leucine transcription factor 2 (BACH2). Transfection of BAC-HIV into 293 T cells resulted in a fourfold difference in production of infectious HIV-1. Cell lines were established that contained BAC-Top2A, BAC-DNMT1, or BAC-BACH2, but only BAC-DNMT1 spontaneously produced virus, albeit at a low level. Stimulation with TNF-{alpha} resulted in virus production from four of five BAC-Top2A and all BAC-DNMT1 cell lines, but not from the BAC-BACH2 lines. The results of these studies highlight differences between integration sites identified in latent T cells to support virus production and reactivation from latency.
- OSTI ID:
- 21486917
- Journal Information:
- Virology, Vol. 410, Issue 1; Other Information: DOI: 10.1016/j.virol.2010.11.001; PII: S0042-6822(10)00705-1; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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