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	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, Chengyu Jiang
Journal	Nature communications (Nat Commun) Vol. 5 Pg. 3594 (May 06 2014) ISSN: 2041-1723 [Electronic] England
PMID	24800825 (Publication Type: Historical Article, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Recombinant Proteins Peptidyl-Dipeptidase A ACE2 protein, human Ace2 protein, mouse Angiotensin-Converting Enzyme 2
Topics	Adolescent Adult Angiotensin-Converting Enzyme 2 Animals Child Child, Preschool Disease Models, Animal Down-Regulation Female History, Ancient Humans Influenza A Virus, H1N1 Subtype Influenza A Virus, H5N1 Subtype (pathogenicity) Influenza, Human (blood, prevention & control, virology) Lung (metabolism, pathology) Lung Injury (drug therapy, genetics) Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Middle Aged Orthomyxoviridae Infections (blood, prevention & control, virology) Peptidyl-Dipeptidase A (biosynthesis, blood, genetics, pharmacology) Recombinant Proteins (pharmacology) Young Adult

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