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Cell Host Microbe. 2008 Aug 14;4(2):134-46. doi: 10.1016/j.chom.2008.06.008.

Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough.

Author information

  • 1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Integrated HIV-1 genomes are found within actively transcribed host genes in latently infected CD4(+) T cells. Readthrough transcription of the host gene might therefore suppress HIV-1 gene expression and promote the latent infection that allows viral persistence in patients on therapy. To address the effect of host gene readthrough, we used homologous recombination to insert HIV-1 genomes in either orientation into an identical position within an intron of an actively transcribed host gene, hypoxanthine-guanine phosphoribosyltransferase (HPRT). Constructs were engineered to permit or block readthrough transcription of HPRT. Readthrough transcription inhibited HIV-1 gene expression for convergently orientated provirus but enhanced HIV-1 gene expression when HIV-1 was in the same orientation as the host gene. Orientation had a >10-fold effect on HIV-1 gene expression. Due to the nature of HIV-1 integration sites in vivo, this orientation-dependent regulation can influence the vast majority of infected cells and adds complexity to the maintenance of latency.

PMID:
18692773
[PubMed - indexed for MEDLINE]
PMCID:
PMC2604135
Free PMC Article

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