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

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Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

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

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