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ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction

Author

Listed:
  • Kei Miyakawa

    (Yokohama City University School of Medicine)

  • Satoko Matsunaga

    (Yokohama City University School of Medicine)

  • Kazuhiko Kanou

    (Infectious Disease Surveillance Center, National Institute of Infectious Diseases)

  • Atsushi Matsuzawa

    (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Ryo Morishita

    (Yokohama City University School of Medicine
    CellFree Sciences Co. Ltd., Ehime University Venture)

  • Ayumi Kudoh

    (Yokohama City University School of Medicine)

  • Keisuke Shindo

    (Graduate School of Medicine, Kyoto University)

  • Masaru Yokoyama

    (Pathogen Genomics Center, National Institute of Infectious Diseases)

  • Hironori Sato

    (Pathogen Genomics Center, National Institute of Infectious Diseases)

  • Hirokazu Kimura

    (Infectious Disease Surveillance Center, National Institute of Infectious Diseases)

  • Tomohiko Tamura

    (Yokohama City University School of Medicine)

  • Naoki Yamamoto

    (National University of Singapore)

  • Hidenori Ichijo

    (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Akifumi Takaori-Kondo

    (Graduate School of Medicine, Kyoto University)

  • Akihide Ryo

    (Yokohama City University School of Medicine)

Abstract

APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin–proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif–ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment.

Suggested Citation

  • Kei Miyakawa & Satoko Matsunaga & Kazuhiko Kanou & Atsushi Matsuzawa & Ryo Morishita & Ayumi Kudoh & Keisuke Shindo & Masaru Yokoyama & Hironori Sato & Hirokazu Kimura & Tomohiko Tamura & Naoki Yamamo, 2015. "ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7945
    DOI: 10.1038/ncomms7945
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