title: A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.
abstract: During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.
authors: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-gasse 7, A-1030 Vienna, Austria.
authors: Keiji
authors: K
authors: Kuba
authors: Yumiko
authors: Y
authors: Imai
authors: Shuan
authors: S
authors: Rao
authors: Hong
authors: H
authors: Gao
authors: Feng
authors: F
authors: Guo
authors: Bin
authors: B
authors: Guan
authors: Yi
authors: Y
authors: Huan
authors: Peng
authors: P
authors: Yang
authors: Yanli
authors: Y
authors: Zhang
authors: Wei
authors: W
authors: Deng
authors: Linlin
authors: L
authors: Bao
authors: Binlin
authors: B
authors: Zhang
authors: Guang
authors: G
authors: Liu
authors: Zhong
authors: Z
authors: Wang
authors: Mark
authors: M
authors: Chappell
authors: Yanxin
authors: Y
authors: Liu
authors: Dexian
authors: D
authors: Zheng
authors: Andreas
authors: A
authors: Leibbrandt
authors: Teiji
authors: T
authors: Wada
authors: Arthur S
authors: AS
authors: Slutsky
authors: Depei
authors: D
authors: Liu
authors: Chuan
authors: C
authors: Qin
authors: Chengyu
authors: C
authors: Jiang
authors: Josef M
authors: JM
authors: Penninger
mesh_terms: D000704:Analysis of Variance; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism*; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D007703:Peptidyl-Dipeptidase A; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000150:complications / Q000201:enzymology*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2