Abstract
Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Lung Injury / drug therapy
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Acute Lung Injury / genetics*
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Acute Lung Injury / mortality
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Acute Lung Injury / virology
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Angiotensin II Type 1 Receptor Blockers / pharmacology*
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Angiotensin II Type 2 Receptor Blockers / pharmacology
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Angiotensin-Converting Enzyme 2
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Animals
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Antiviral Agents / pharmacology*
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Gene Expression
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Humans
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Imidazoles / pharmacology
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Influenza A Virus, H7N9 Subtype / drug effects
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Influenza A Virus, H7N9 Subtype / pathogenicity
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Influenza A Virus, H7N9 Subtype / physiology
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Losartan / pharmacology*
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Lung / drug effects
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Lung / metabolism
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Lung / pathology
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Lung / virology
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Mice
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Mice, Inbred C57BL
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Orthomyxoviridae Infections / drug therapy
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Orthomyxoviridae Infections / genetics*
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Orthomyxoviridae Infections / mortality
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Orthomyxoviridae Infections / virology
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Peptidyl-Dipeptidase A / deficiency
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Peptidyl-Dipeptidase A / genetics*
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Pyridines / pharmacology
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Receptor, Angiotensin, Type 1 / genetics
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Receptor, Angiotensin, Type 1 / metabolism
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Receptor, Angiotensin, Type 2 / genetics
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Receptor, Angiotensin, Type 2 / metabolism
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Signal Transduction
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Survival Analysis
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Viral Load / drug effects
Substances
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Angiotensin II Type 1 Receptor Blockers
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Angiotensin II Type 2 Receptor Blockers
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Antiviral Agents
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Imidazoles
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Pyridines
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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PD 123319
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Ace2 protein, mouse
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Angiotensin-Converting Enzyme 2
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Losartan