Cleavage of group 1 coronavirus spike proteins: how furin cleavage is traded off against heparan sulfate binding upon cell culture adaptation.
A longstanding enigmatic feature of the group 1 coronaviruses is the uncleaved phenotype of their spike protein, an exceptional property among class I fusion proteins. Here, however, we show that some group 1 coronavirus spike proteins carry a furin enzyme recognition motif and can actually be cleaved, as demonstrated for a feline coronavirus. Interestingly, this feature can be lost during cell culture adaptation by a single mutation in the cleavage motif; this, however, preserves a heparan sulfate binding motif and renders infection by the virus heparan sulfate dependent. We identified a similar cell culture adaptation for the human coronavirus OC43.
de Haan
C A M
CA
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medcine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
Haijema
B J
BJ
Schellen
P
P
Wichgers Schreur
P
P
te Lintelo
E
E
Vennema
H
H
Rottier
P J M
PJ
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D002460:Cell Line; D045683:Furin / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
D045683:Furin; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins