Influence of host gene transcription level and orientation on HIV-1 latency in a primary-cell model
Journal
Journal of Virology
Journal Volume
85
Journal Issue
11
Pages
5384-5393
Date Issued
2011
Author(s)
Shan L
Rabi S.A
Bravo H.C
Shroff N.S
Irizarry R.A
Zhang H
Margolick J.B
Siliciano J.D
Siliciano R.F.
Abstract
Human immunodeficiency virus type 1 (HIV-1) establishes a latent reservoir in resting memory CD4 +T cells. This latent reservoir is a major barrier to the eradication of HIV-1 in infected individuals and is not affected by highly active antiretroviral therapy (HAART). Reactivation of latent HIV-1 is a possible strategy for elimination of this reservoir. The mechanisms with which latency is maintained are unclear. In the analysis of the regulation of HIV-1 gene expression, it is important to consider the nature of HIV-1 integration sites. In this study, we analyzed the integration and transcription of latent HIV-1 in a primary CD4 + T cell model of latency. The majority of integration sites in latently infected cells were in introns of transcription units. Serial analysis of gene expression (SAGE) demonstrated that more than 90% of those host genes harboring a latent integrated provirus were transcriptionally active, mostly at high levels. For latently infected cells, we observed a modest preference for integration in the same transcriptional orientation as the host gene (63.8% versus 36.2%). In contrast, this orientation preference was not observed in acutely infected or persistently infected cells. These results suggest that transcriptional interference may be one of the important factors in the establishment and maintenance of HIV-1 latency. Our findings suggest that disrupting the negative control of HIV-1 transcription by upstream host promoters could facilitate the reactivation of latent HIV-1 in some resting CD4 + T cells. ? 2011, American Society for Microbiology.
SDGs
Other Subjects
article; CD4+ T lymphocyte; controlled study; gene expression regulation; genetic transcription; human; human cell; Human immunodeficiency virus 1; intron; nonhuman; priority journal; serial analysis of gene expression; upregulation; virus DNA cell DNA interaction; virus latency; virus transcription; CD4-Positive T-Lymphocytes; Cells, Cultured; Gene Expression Profiling; Gene Expression Regulation, Viral; HIV-1; Humans; Transcription, Genetic; Virus Integration; Virus Latency; Human immunodeficiency virus 1
Type
journal article