title: Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections.
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.
authors.affiliation: 1] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China [2].
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zou
authors.affiliation: 1] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China [2].
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: 1] 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, Beijing 102206, China [2].
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.affiliation: 1] 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, Beijing 102206, China [2].
authors.forename: Rongbao
authors.initials: R
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Xiangwu
authors.initials: X
authors.lastname: Ju
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: 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, Beijing 102206, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Zongsheng
authors.initials: Z
authors.lastname: Han
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Jindong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Huandi
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Huang
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.affiliation: Genetic Engineering Laboratory, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130062, China.
authors.forename: Ningyi
authors.initials: N
authors.lastname: Jin
authors.affiliation: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, Vienna A-1030, Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: 1] State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China [2] Center for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D049690:History, Ancient; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000097:blood / Q000517:prevention & control / Q000821:virology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000517:prevention & control* / Q000821:virology; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2