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

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, Chang Li, Huijun Lu, Ning Li, Dangsheng Li, Ningyi Jin (), Josef M. Penninger () and Chengyu Jiang ()
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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

Nature Communications, 2014, vol. 5, issue 1, 1-7

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4594

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