Orientation-Dependent Regulation of Integrated HIV-1 Expression by Host Gene Transcriptional Readthrough

Yefei Han, Yijie B. Lin, Wenfeng An, Jie Xu, Hung Chih Yang, Karen O'Connell, Dominic Dordai, Jef D. Boeke, Janet M Siliciano, Robert F Siliciano

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)134-146
Number of pages13
JournalCell Host and Microbe
Volume4
Issue number2
DOIs
StatePublished - Aug 14 2008

Fingerprint

HIV-1
Gene Expression
Genes
Genome
Hypoxanthine Phosphoribosyltransferase
Proviruses
Homologous Recombination
Virus Diseases
Introns
Maintenance

Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Orientation-Dependent Regulation of Integrated HIV-1 Expression by Host Gene Transcriptional Readthrough. / Han, Yefei; Lin, Yijie B.; An, Wenfeng; Xu, Jie; Yang, Hung Chih; O'Connell, Karen; Dordai, Dominic; Boeke, Jef D.; Siliciano, Janet M; Siliciano, Robert F.

In: Cell Host and Microbe, Vol. 4, No. 2, 14.08.2008, p. 134-146.

Research output: Contribution to journalArticle

Han, Yefei ; Lin, Yijie B. ; An, Wenfeng ; Xu, Jie ; Yang, Hung Chih ; O'Connell, Karen ; Dordai, Dominic ; Boeke, Jef D. ; Siliciano, Janet M ; Siliciano, Robert F. / Orientation-Dependent Regulation of Integrated HIV-1 Expression by Host Gene Transcriptional Readthrough. In: Cell Host and Microbe. 2008 ; Vol. 4, No. 2. pp. 134-146.
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