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Journal of Virology, June 2008, p. 6078-6083, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00074-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cleavage of Group 1 Coronavirus Spike Proteins: How Furin Cleavage Is Traded Off against Heparan Sulfate Binding upon Cell Culture Adaptation{triangledown}

C. A. M. de Haan,{dagger} B. J. Haijema,{dagger},§ P. Schellen, P. Wichgers Schreur, E. te Lintelo, H. Vennema,{ddagger} and P. J. M. Rottier*

Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands

Received 11 January 2008/ Accepted 31 March 2008

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.


* Corresponding author. Mailing address: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medcine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands. Phone: 31-30-2532462. Fax: 31-30-2536723. E-mail: P.Rottier{at}uu.nl

{triangledown} Published ahead of print on 9 April 2008.

{dagger} These authors contributed equally.

§ Present address: Intervet Nederland B.V., Postbus 50, 5830 AB Boxmeer, The Netherlands.

{ddagger} Present address: Center for Infectious Diseases Control, National Institute for Public Health and the Environment (RIVM), Postbus 1, 3720 BA Bilthoven, The Netherlands.


Journal of Virology, June 2008, p. 6078-6083, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00074-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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