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

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

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.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Child
  • Child, Preschool
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • History, Ancient
  • Humans
  • 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
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • 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
  • Young Adult

Substances

  • Recombinant Proteins
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2