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The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein

Author

Listed:
  • Kei Miyakawa

    (Yokohama City University School of Medicine)

  • Mayuko Nishi

    (Yokohama City University School of Medicine)

  • Satoko Matsunaga

    (Yokohama City University School of Medicine)

  • Akiko Okayama

    (Advanced Medical Research Center, Yokohama City University)

  • Masaki Anraku

    (Yokohama City University School of Medicine)

  • Ayumi Kudoh

    (Yokohama City University School of Medicine)

  • Hisashi Hirano

    (Advanced Medical Research Center, Yokohama City University)

  • Hirokazu Kimura

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

  • Yuko Morikawa

    (Kitasato Institute for Life Sciences and Graduate School for Infection Control, Kitasato University)

  • Naoki Yamamoto

    (National University of Singapore)

  • Akira Ono

    (University of Michigan Medical School)

  • Akihide Ryo

    (Yokohama City University School of Medicine)

Abstract

Diverse cellular proteins and RNAs are tightly regulated in their subcellular localization to exert their local function. Here we report that the tumour suppressor adenomatous polyposis coli protein (APC) directs the localization and assembly of human immunodeficiency virus (HIV)-1 Gag polyprotein at distinct membrane components to enable the efficient production and spread of infectious viral particles. A proteomic analysis and subsequent biomolecular interaction assay reveals that the carboxyl terminus of APC interacts with the matrix region of Gag. Ectopic expression of APC, but not its familial adenomatous polyposis-related truncation mutant, prominently enhances HIV-1 production. Conversely, the depletion of APC leads to a significant decrease in membrane targeting of viral components, resulting in the severe loss of production of infectious virions. Furthermore, APC promotes the directional assembly of viral components at virological synapses, thereby facilitating cell-to-cell viral transmission. These findings reveal an unexpected role of APC in the directional spread of HIV-1.

Suggested Citation

  • Kei Miyakawa & Mayuko Nishi & Satoko Matsunaga & Akiko Okayama & Masaki Anraku & Ayumi Kudoh & Hisashi Hirano & Hirokazu Kimura & Yuko Morikawa & Naoki Yamamoto & Akira Ono & Akihide Ryo, 2017. "The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14259
    DOI: 10.1038/ncomms14259
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