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.

我所蔣澄宇課題組聯(lián)合金寧一課題組等國內(nèi)外相關(guān)人員研究論文“Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections”于2014年5月7號在線發(fā)表于Nature Communications雜志（Nat Commun. 2014 May 6;5:3594.），該項(xiàng)研究發(fā)現(xiàn)高致病性H5N1病毒感染導(dǎo)致會患者血漿中血管緊張素2（AngII）的表達(dá)水平極其顯著地升高，并可能與疾病的嚴(yán)重程度和致死率相關(guān)。H5N1感染小鼠模型可以導(dǎo)致小鼠肺部的血管緊張素轉(zhuǎn)化酶2（ACE2）表達(dá)水平下調(diào)并伴隨AngII的顯著升高，ACE2基因缺失的小鼠感染H5N1病毒后會導(dǎo)致更為嚴(yán)重的急性呼吸窘迫綜合癥癥狀，而通過外源性地注射ACE2重組蛋白則可以顯著緩解急性呼吸窘迫綜合癥癥狀。以上研究將ACE2與H5N1導(dǎo)致的急性呼吸窘迫綜合癥相關(guān)聯(lián)，并為未來可能的流感爆發(fā)提供了潛在的治療策略。