Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63

被引:376
作者
Glowacka, Ilona [1 ]
Bertram, Stephanie [1 ]
Herzog, Petra [2 ,3 ]
Pfefferle, Susanne [2 ]
Steffen, Imke [1 ]
Muench, Marcus O. [4 ,5 ]
Simmons, Graham [4 ,5 ]
Hofmann, Heike [6 ]
Kuri, Thomas [7 ]
Weber, Friedemann [7 ]
Eichler, Jutta [8 ]
Drosten, Christian [9 ]
Poehlmann, Stefan [1 ]
机构
[1] Hannover Med Sch, Inst Virol, D-30625 Hannover, Germany
[2] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany
[3] Qiagen Hamburg GmbH, D-22767 Hamburg, Germany
[4] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA
[6] Univ Kiel, Dept Med Microbiol & Virol, D-24105 Kiel, Germany
[7] Univ Freiburg, Dept Virol, D-79008 Freiburg, Germany
[8] Univ Erlangen Nurnberg, Dept Med Chem, D-91052 Erlangen, Germany
[9] Univ Bonn, Med Ctr, Inst Virol, D-53127 Bonn, Germany
关键词
ANGIOTENSIN-CONVERTING ENZYME-2; SARS-COV; FUNCTIONAL RECEPTOR; TISSUE DISTRIBUTION; INFECTION; ANGIOTENSIN-CONVERTING-ENZYME-2; CHILDREN; PATHOGENESIS; EXPRESSION; DISEASE;
D O I
10.1128/JVI.01248-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 down-regulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.
引用
收藏
页码:1198 / 1205
页数:8
相关论文
共 34 条
[1]   Human airway epithelial cell culture to identify new respiratory viruses: Coronavirus NL63 as a model [J].
Banach, Bridget S. ;
Orenstein, Jan M. ;
Fox, Linda M. ;
Randell, Scott H. ;
Rowley, Anne H. ;
Baker, Susan C. .
JOURNAL OF VIROLOGICAL METHODS, 2009, 156 (1-2) :19-26
[2]   Human coronavirus NL63 infection in Canada [J].
Bastien, N ;
Anderson, K ;
Hart, L ;
Van Caeseele, P ;
Brandt, K ;
Milley, D ;
Hatchette, T ;
Weiss, EC ;
Li, Y .
JOURNAL OF INFECTIOUS DISEASES, 2005, 191 (04) :503-506
[3]   Human coronavirus NL63 infection and other coronavirus infections in children hospitalized with acute respiratory disease in Hong Kong, China [J].
Chiu, SS ;
Chan, KH ;
Chu, KW ;
Kwan, SW ;
Guan, Y ;
Poon, LLM ;
Peiris, JSM .
CLINICAL INFECTIOUS DISEASES, 2005, 40 (12) :1721-1729
[4]   Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways [J].
Ding, YQ ;
He, L ;
Zhang, QL ;
Huang, ZX ;
Che, XY ;
Hou, JL ;
Wang, HJ ;
Shen, H ;
Qiu, LW ;
Li, ZG ;
Geng, J ;
Cai, JJ ;
Han, HX ;
Li, X ;
Kang, W ;
Weng, DS ;
Liang, P ;
Jiang, SB .
JOURNAL OF PATHOLOGY, 2004, 203 (02) :622-630
[5]   Systematic Assembly of a Full-Length Infectious Clone of Human Coronavirus NL63 [J].
Donaldson, Eric F. ;
Yount, Boyd ;
Sims, Amy C. ;
Burkett, Susan ;
Pickles, Raymond J. ;
Baric, Ralph S. .
JOURNAL OF VIROLOGY, 2008, 82 (23) :11948-11957
[6]   Detection of human coronavirus NL63 in young children with bronchiolitis [J].
Ebihara, T ;
Endo, R ;
Ma, XM ;
Ishiguro, N ;
Kikuta, H .
JOURNAL OF MEDICAL VIROLOGY, 2005, 75 (03) :463-465
[7]   A previously undescribed coronavirus associated with respiratory disease in humans [J].
Fouchier, RAM ;
Hartwig, NG ;
Bestebroer, TM ;
Niemeyer, B ;
de Jong, JC ;
Simon, JH ;
Osterhaus, ADME .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (16) :6212-6216
[8]   Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry [J].
Haga, Shiori ;
Yamamoto, Norio ;
Nakai-Murakami, Chikako ;
Osawa, Yoshiaki ;
Tokunaga, Kenzo ;
Sata, Tetsutaro ;
Yamamoto, Naoki ;
Sasazuki, Takehiko ;
Ishizaka, Yukihito .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (22) :7809-7814
[9]   Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis [J].
Hamming, I ;
Timens, W ;
Bulthuis, MLC ;
Lely, AT ;
Navis, GJ ;
van Goor, H .
JOURNAL OF PATHOLOGY, 2004, 203 (02) :631-637
[10]   Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry [J].
Hofmann, H ;
Pyrc, K ;
van der Hoek, L ;
Geier, M ;
Berkhout, B ;
Pöhlmann, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (22) :7988-7993