title: Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus.
abstract: Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV-infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV-induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease.
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Gu
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics, Capital Medical University; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.
authors.forename: Zhengde
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Chinese PLA General Hospital, 1000853, China.
authors.forename: Tieling
authors.initials: T
authors.lastname: Li
authors.affiliation: Beijing302 Hospital, Beijing, 100039, China.
authors.forename: Shaogeng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Chengcai
authors.initials: C
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Keyu
authors.initials: K
authors.lastname: Wang
authors.affiliation: Chinese PLA General Hospital, 1000853, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Han
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yueqiang
authors.initials: Y
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.affiliation: Beijing302 Hospital, Beijing, 100039, China.
authors.forename: Peirui
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Beijing302 Hospital, Beijing, 100039, China.
authors.forename: Zhouhai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing302 Hospital, Beijing, 100039, China.
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, CVC4926, Cincinnati, OH 45267, USA.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.|Beijing302 Hospital, Beijing, 100039, China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Yang
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004195:Disease Models, Animal; D055370:Lung Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012720:Severity of Illness Index
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2
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