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<p>Human immunodeficiency virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its life cycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we used a combination of ribosome profiling, disome sequencing and RNA sequencing. We show that HIV-1 messenger RNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in the translational efficiency of host genes that are implicated in host cell translation. Our data identify upstream open reading frames in the HIV-1 5′-untranslated region as well as internal open reading frames in the <i>Vif</i> and <i>Pol</i> coding domains. We also observed ribosomal collisions in <i>Gag-Pol</i> upstream of the ribosome frameshift site that we attributed to an RNA structural fold using RNA structural probing and functional analysis. Antisense oligonucleotides designed to alter the base of this structure decreased frameshift efficiency. Overall, our data highlight the complexity of HIV-1 gene regulation and provide a key resource for decoding of host–pathogen interactions upon HIV-1 infection. Furthermore, we provide evidence for a RNA structural fold including the frameshift site that could serve as a target for antiviral therapy.</p>

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The translational landscape of HIV-1 infected cells reveals key gene regulatory principles

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月15日

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  • Anuja Kibe,
  • Stefan Buck,
  • Anne-Sophie Gribling-Burrer,
  • Orian Gilmer,
  • Patrick Bohn,
  • Tatyana Koch,
  • Chiara Noemi-Marie Mireisz,
  • Andreas Schlosser,
  • Florian Erhard,
  • Redmond P. Smyth,
  • Neva Caliskan

摘要

Human immunodeficiency virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its life cycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we used a combination of ribosome profiling, disome sequencing and RNA sequencing. We show that HIV-1 messenger RNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in the translational efficiency of host genes that are implicated in host cell translation. Our data identify upstream open reading frames in the HIV-1 5′-untranslated region as well as internal open reading frames in the Vif and Pol coding domains. We also observed ribosomal collisions in Gag-Pol upstream of the ribosome frameshift site that we attributed to an RNA structural fold using RNA structural probing and functional analysis. Antisense oligonucleotides designed to alter the base of this structure decreased frameshift efficiency. Overall, our data highlight the complexity of HIV-1 gene regulation and provide a key resource for decoding of host–pathogen interactions upon HIV-1 infection. Furthermore, we provide evidence for a RNA structural fold including the frameshift site that could serve as a target for antiviral therapy.