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A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.
Nat Med. 2005 Aug; 11(8):875-9.NMed

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+Show Affiliations

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-gasse 7, A-1030 Vienna, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16007097

Citation

Kuba, Keiji, et al. "A Crucial Role of Angiotensin Converting Enzyme 2 (ACE2) in SARS Coronavirus-induced Lung Injury." Nature Medicine, vol. 11, no. 8, 2005, pp. 875-9.
Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875-9.
Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., Bao, L., Zhang, B., Liu, G., Wang, Z., Chappell, M., Liu, Y., Zheng, D., Leibbrandt, A., Wada, T., ... Penninger, J. M. (2005). A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nature Medicine, 11(8), 875-9.
Kuba K, et al. A Crucial Role of Angiotensin Converting Enzyme 2 (ACE2) in SARS Coronavirus-induced Lung Injury. Nat Med. 2005;11(8):875-9. PubMed PMID: 16007097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. AU - Kuba,Keiji, AU - Imai,Yumiko, AU - Rao,Shuan, AU - Gao,Hong, AU - Guo,Feng, AU - Guan,Bin, AU - Huan,Yi, AU - Yang,Peng, AU - Zhang,Yanli, AU - Deng,Wei, AU - Bao,Linlin, AU - Zhang,Binlin, AU - Liu,Guang, AU - Wang,Zhong, AU - Chappell,Mark, AU - Liu,Yanxin, AU - Zheng,Dexian, AU - Leibbrandt,Andreas, AU - Wada,Teiji, AU - Slutsky,Arthur S, AU - Liu,Depei, AU - Qin,Chuan, AU - Jiang,Chengyu, AU - Penninger,Josef M, Y1 - 2005/07/10/ PY - 2005/04/22/received PY - 2005/06/03/accepted PY - 2005/7/12/pubmed PY - 2005/12/24/medline PY - 2005/7/12/entrez SP - 875 EP - 9 JF - Nature medicine JO - Nat Med VL - 11 IS - 8 N2 - 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. SN - 1078-8956 UR - https://www.unboundmedicine.com/medline/citation/16007097/full_citation L2 - https://doi.org/10.1038/nm1267 DB - PRIME DP - Unbound Medicine ER -