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A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection

Author

Listed:
  • Yoichiro Fujioka

    (Hokkaido University Graduate School of Medicine, N15W7, Sapporo 060-8638, Japan)

  • Masumi Tsuda

    (Hokkaido University Graduate School of Medicine, N15W7, Sapporo 060-8638, Japan)

  • Asuka Nanbo

    (Hokkaido University Graduate School of Medicine, N15W7, Sapporo 060-8638, Japan)

  • Tomoe Hattori

    (Hokkaido University Research Centre for Zoonosis Control, N20W10, Sapporo 060-0020, Japan)

  • Junko Sasaki

    (Akita University Graduate School of Medicine)

  • Takehiko Sasaki

    (Akita University Graduate School of Medicine)

  • Tadaaki Miyazaki

    (Hokkaido University Research Centre for Zoonosis Control, N20W10, Sapporo 060-0020, Japan
    Present address: Research Section of Probiotics Immunology, Institute for Genetic Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan)

  • Yusuke Ohba

    (Hokkaido University Graduate School of Medicine, N15W7, Sapporo 060-8638, Japan)

Abstract

Various viruses enter host cells via endocytosis, but the molecular mechanisms underlying the specific internalization pathways remain unclear. Here we show that influenza A viruses (IAVs) enter cells via redundant pathways of clathrin-mediated and clathrin-independent endocytosis, with intracellular Ca2+ having a central role in regulation of both pathways by activating a signalling axis comprising RhoA, Rho-kinase, phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and phospholipase C (PLC). IAV infection induces oscillations in the cytosolic Ca2+ concentration of host cells, the prevention of which markedly attenuates virus internalization and infection. The small GTPase RhoA is found both to function downstream of the virus-induced Ca2+ response and itself to induce Ca2+ oscillations in a manner dependent on Rho-kinase and subsequent PIP5K-PLC signalling. This signalling circuit regulates both clathrin-mediated and clathrin-independent endocytosis during virus infection and seems to constitute a key mechanism for regulation of IAV internalization and infection.

Suggested Citation

  • Yoichiro Fujioka & Masumi Tsuda & Asuka Nanbo & Tomoe Hattori & Junko Sasaki & Takehiko Sasaki & Tadaaki Miyazaki & Yusuke Ohba, 2013. "A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection," Nature Communications, Nature, vol. 4(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3763
    DOI: 10.1038/ncomms3763
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