title: Downregulation of angiotensin-converting enzyme 2 by the neuraminidase protein of influenza A (H1N1) virus.
abstract: Influenza A (H1N1) virus, a high-risk infectious pathogen, can cause severe acute lung injury leading to significant morbidity and mortality. Angiotensin-converting enzyme 2 (ACE2), a negative regulator of the renin-angiotensin system (RAS), plays a protective role in pathogenesis of acute lung injury. Here, we showed that ACE2 protein levels were significantly downregulated after infection with H1N1 viruses but was dispensable for viral replication. ACE2 protein downregulation was most likely related to ACE2 protein degradation by proteasome pathway rather than ACE2 shedding. Finally, we found that ACE2 cleavage could be regulated by influenza neuraminidase (NA), which was fundamentally different from the classically sheddase-induced proteolytic cleavage of ACE2.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. Electronic address: merryliuxin@gmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Viral Diseases, NIAID, Bethesda, MD 20892, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: Institute of Basic Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Institute of Basic Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Deyan
authors.initials: D
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D015536:Down-Regulation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D007251:Influenza, Human / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
keywords: ACE2; Downregulation; Influenza; Neuraminidase