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.
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.