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 D. 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

    Keywords

    • MICROBIO
    • MOLIMMUNO

    ASJC Scopus subject areas

    • Parasitology
    • Microbiology
    • Virology

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