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

• Published in: Nature communications 2014-05, Vol.5 (1), p.3594-3594, Article 3594
• Main Authors: Zou, Zhen, Yan, Yiwu, Shu, Yuelong, Gao, Rongbao, Sun, Yang, Li, Xiao, Ju, Xiangwu, Liang, Zhu, Liu, Qiang, Zhao, Yan, Guo, Feng, Bai, Tian, Han, Zongsheng, Zhu, Jindong, Zhou, Huandi, Huang, Fengming, Li, Chang, Lu, Huijun, Li, Ning, Li, Dangsheng, Jin, Ningyi, Penninger, Josef M., Jiang, Chengyu
• Format: Article
• Language: English
• Subjects: 13/95; 38; 631/326/596/1578; 64/60; 692/308; 692/699/1785; 82/80; Adolescent; Adult; Animals; Avian flu; Birds; Child; Child, Preschool; Disease Models, Animal; Down-Regulation; Enzymes; Female; History, Ancient; Humanities and Social Sciences; Humans; Infections; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype - pathogenicity; Influenza, Human - blood; Influenza, Human - prevention & control; Influenza, Human - virology; Lung - metabolism; Lung - pathology; Lung Injury - drug therapy; Lung Injury - genetics; Lungs; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Molecular biology; multidisciplinary; Orthomyxoviridae Infections - blood; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Peptidyl-Dipeptidase A - biosynthesis; Peptidyl-Dipeptidase A - blood; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - pharmacology; Recombinant Proteins - pharmacology; Science; Science (multidisciplinary); Sepsis; Viruses; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4594

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. H5N1 avian influenza viruses can be highly pathogenic. Here, the authors show that H5N1 infection leads to increased serum levels of angiotensin II in patients and mice, and that administration of angiotensin-converting enzyme 2 ameliorates lung injury in infected mice.