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

Zou Z1, Yan Y1, Shu Y2, Gao R2, Sun Y3, Li X4, Ju X3, Liang Z3, Liu Q3, Zhao Y3, Guo F3, Bai T5, Han Z3, Zhu J3, Zhou H3, Huang F3, Li C4, Lu H4, Li N3, Li D6, Jin N4, Penninger JM7, Jiang C8

Nat Commun. 2014 May 6;5:3594. doi: 10.1038/ncomms4594.
PMID: 24800825

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.

我所蒋澄宇课题组联合金宁一课题组等国内外相关人员研究论文“Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections”于2014年5月7号在线发表于Nature Communications杂志（Nat Commun. 2014 May 6;5:3594.），该项研究发现高致病性H5N1病毒感染导致会患者血浆中血管紧张素2（AngII）的表达水平极其显著地升高，并可能与疾病的严重程度和致死率相关。H5N1感染小鼠模型可以导致小鼠肺部的血管紧张素转化酶2（ACE2）表达水平下调并伴随AngII的显著升高，ACE2基因缺失的小鼠感染H5N1病毒后会导致更为严重的急性呼吸窘迫综合症症状，而通过外源性地注射ACE2重组蛋白则可以显著缓解急性呼吸窘迫综合症症状。以上研究将ACE2与H5N1导致的急性呼吸窘迫综合症相关联，并为未来可能的流感爆发提供了潜在的治疗策略。