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RPLP1 restricts HIV-1 transcription by disrupting C/EBPβ binding to the LTR

Author

Listed:
  • Weijing Yang

    (The First Hospital of Jilin University
    The First Hospital of Jilin University
    The First Hospital of Jilin University)

  • Hong Wang

    (The First Hospital of Jilin University
    The First Hospital of Jilin University
    The First Hospital of Jilin University)

  • Zhaolong Li

    (The First Hospital of Jilin University
    The First Hospital of Jilin University
    The First Hospital of Jilin University)

  • Lihua Zhang

    (Chinese Academy of Science)

  • Jianhui Liu

    (Chinese Academy of Science)

  • Frank Kirchhoff

    (Ulm University Medical Center)

  • Chen Huan

    (The First Hospital of Jilin University
    The First Hospital of Jilin University
    The First Hospital of Jilin University)

  • Wenyan Zhang

    (The First Hospital of Jilin University
    The First Hospital of Jilin University
    The First Hospital of Jilin University)

Abstract

Long-term non-progressors (LTNPs) of HIV-1 infection may provide important insights into mechanisms involved in viral control and pathogenesis. Here, our results suggest that the ribosomal protein lateral stalk subunit P1 (RPLP1) is expressed at higher levels in LTNPs compared to regular progressors (RPs). Functionally, RPLP1 inhibits transcription of clade B HIV-1 strains by occupying the C/EBPβ binding sites in the viral long terminal repeat (LTR). This interaction requires the α-helixes 2 and 4 domains of RPLP1 and is evaded by HIV-1 group M subtype C and group N, O and P strains that do not require C/EBPβ for transcription. We further demonstrate that HIV-1-induced translocation of RPLP1 from the cytoplasm to the nucleus is essential for antiviral activity. Finally, knock-down of RPLP1 promotes reactivation of latent HIV-1 proviruses. Thus, RPLP1 may play a role in the maintenance of HIV-1 latency and resistance to RPLP1 restriction may contribute to the effective spread of clade C HIV-1 strains.

Suggested Citation

  • Weijing Yang & Hong Wang & Zhaolong Li & Lihua Zhang & Jianhui Liu & Frank Kirchhoff & Chen Huan & Wenyan Zhang, 2024. "RPLP1 restricts HIV-1 transcription by disrupting C/EBPβ binding to the LTR," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49622-1
    DOI: 10.1038/s41467-024-49622-1
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    2. Stuart J. D. Neil & Trinity Zang & Paul D. Bieniasz, 2008. "Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu," Nature, Nature, vol. 451(7177), pages 425-430, January.
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