Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
The Department of Microbiology
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Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
The Department of Microbiology

Research

  • Research
  • Mechanism of Activation of Respiratory Viruses by Host Proteases

Mechanism of Activation of Respiratory Viruses by Host Proteases

Many viruses have spikes (spike proteins) on the surface of their particles. We have shown that the spike proteins of various respiratory viruses, such as influenza virus and novel coronavirus (SARS-CoV-2), are activated (dramatically increasing infection efficiency) by a protease called TMPRSS2 in the host cell where the virus infects. These results have contributed to the elucidation of the pathogenic mechanism of SARS-CoV-2, countermeasures, vaccine development, and therapeutic drug development. We plan to continue further research on the pathogenesis of respiratory viruses in order to deepen our understanding of respiratory viruses and to prepare for the emergence of new pandemic viruses in the future.



Main Related Publications

  1. Iwata-Yoshikawa N, Kakizaki M, Shiwa-Sudo N, Okura T, Tahara M, Fukushi S, Maeda K, Kawase M, Asanuma H, Tomita Y, Takayama I, Matsuyama S, Shirato K, Suzuki T, Nagata N*, Takeda M*. Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways. Nat Commun 13: 6100, 2022.
  2. Tomita Y, Matsuyama S, Fukuhara H, Maenaka K, Kataoka H, Hashiguchi T, Takeda M*: The physiological TMPRSS2 inhibitor HAI–2 alleviates SARS-CoV-2 infection. J Virol 95:e00434–21, 2021.
  3. Matsuyama S*, Nao N, Shirato K, Kawase M, Saito S, Takayama I, Nagata N, Sekizuka T, Katoh H, Kato F, Sakata M, Tahara M, Kutsuna S, Ohmagari N, Kuroda M, Suzuki T, Kageyama T, Takeda M*: Enhanced isolation of SARS-CoV-2 by TMPRSS2–expressing cells. Proc Natl Acad Sci U S A 117:7001–7003, 2020.
  4. Iwata–Yoshikawa N, Okamura T, Shimizu Y, Hasegawa H, Takeda M, Nagata N*: TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J Virol 93:e01815–18, 2019.
  5. Sakai K, Ami Y, Tahara M, Kubota T, Anraku M, Abe M, Nakajima N, Sekizuka T, Shirato K, Suzaki Y, Ainai A, Nakatsu Y, Kanou K, Nakamura K, Suzuki T, Komase K, Nobusawa E, Maenaka K, Kuroda M, Hasegawa H, Kawaoka Y, Tashiro M, Takeda M*: The host protease TMPRSS2 plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses. J Virol 88:5608–5616, 2014.