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Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections

Author

Listed:
  • Zhen Zou

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Yiwu Yan

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Yuelong Shu

    (Key Laboratory for Medical Virology of National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, Changbai 155, Changping District)

  • Rongbao Gao

    (Key Laboratory for Medical Virology of National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, Changbai 155, Changping District)

  • Yang Sun

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Xiao Li

    (Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences)

  • Xiangwu Ju

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Zhu Liang

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Qiang Liu

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Yan Zhao

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Feng Guo

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Tian Bai

    (Key Laboratory for Medical Virology of National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, Changbai 155, Changping District)

  • Zongsheng Han

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Jindong Zhu

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Huandi Zhou

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Fengming Huang

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Chang Li

    (Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences)

  • Huijun Lu

    (Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences)

  • Ning Li

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University)

  • Dangsheng Li

    (Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

  • Ningyi Jin

    (Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences)

  • Josef M. Penninger

    (IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3)

  • Chengyu Jiang

    (State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University
    Center for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences)

Abstract

The potential for avian influenza H5N1 outbreaks has increased in recent years. Thus, it is paramount to develop novel strategies to alleviate death rates. Here we show that avian influenza A H5N1-infected patients exhibit markedly increased serum levels of angiotensin II. High serum levels of angiotensin II appear to be linked to the severity and lethality of infection, at least in some patients. In experimental mouse models, infection with highly pathogenic avian influenza A H5N1 virus results in downregulation of angiotensin-converting enzyme 2 (ACE2) expression in the lung and increased serum angiotensin II levels. Genetic inactivation of ACE2 causes severe lung injury in H5N1-challenged mice, confirming a role of ACE2 in H5N1-induced lung pathologies. Administration of recombinant human ACE2 ameliorates avian influenza H5N1 virus-induced lung injury in mice. Our data link H5N1 virus-induced acute lung failure to ACE2 and provide a potential treatment strategy to address future flu pandemics.

Suggested Citation

  • Zhen Zou & Yiwu Yan & Yuelong Shu & Rongbao Gao & Yang Sun & Xiao Li & Xiangwu Ju & Zhu Liang & Qiang Liu & Yan Zhao & Feng Guo & Tian Bai & Zongsheng Han & Jindong Zhu & Huandi Zhou & Fengming Huang , 2014. "Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections," Nature Communications, Nature, vol. 5(1), pages 1-7, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4594
    DOI: 10.1038/ncomms4594
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    Cited by:

    1. Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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