Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury.
Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks.
1] State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China [2] Beijing 302 Hospital, Beijing, 100039, China.
Penghui
P
Yang
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Hongjing
H
Gu
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Zhongpeng
Z
Zhao
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.
Wei
W
Wang
Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, China.
Bin
B
Cao
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Chengcai
C
Lai
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Xiaolan
X
Yang
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
LiangYan
L
Zhang
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Yueqiang
Y
Duan
Beijing 302 Hospital, Beijing, 100039, China.
Shaogeng
S
Zhang
Quanzhou First Hospital, Fujian 362321, China.
Weiwen
W
Chen
Quanzhou First Hospital, Fujian 362321, China.
Wenbo
W
Zhen
Shishi Hospital, Fujian 362700, China.
Maosheng
M
Cai
Institute of Molecular Biotechnology in the Austrian Academy of Sciences, Vienna, A-1030, Austria.
Josef M
JM
Penninger
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.
Chengyu
C
Jiang
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Xiliang
X
Wang
D055371:Acute Lung Injury / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000821:virology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D064766:Influenza A Virus, H7N9 Subtype / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D019808:Losartan / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000821:virology; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D019562:Viral Load / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000998:Antiviral Agents; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D019808:Losartan