Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63.
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 downregulation 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.
Institute of Virology, OE 5230, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Ilona
I
Glowacka
Stephanie
S
Bertram
Petra
P
Herzog
Susanne
S
Pfefferle
Imke
I
Steffen
Marcus O
MO
Muench
Graham
G
Simmons
Heike
H
Hofmann
Thomas
T
Kuri
Friedemann
F
Weber
Jutta
J
Eichler
Christian
C
Drosten
Stefan
S
Pöhlmann
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D017934:Coronavirus / Q000378:metabolism / Q000472:pathogenicity*; D015536:Down-Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism / Q000472:pathogenicity*; D064370:Spike Glycoprotein, Coronavirus; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2