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Journal of Virology, December 2007, p. 13378-13384, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01170-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Proteolysis of the Ebola Virus Glycoproteins Enhances Virus Binding and Infectivity{triangledown}

Rachel L. Kaletsky, Graham Simmons,{dagger} and Paul Bates*

Department of Microbiology, University of Pennsylvania School of Medicine, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104-6076

Received 29 May 2007/ Accepted 25 September 2007

Cellular cathepsins are required for Ebola virus infection and are believed to proteolytically process the Ebola virus glycoprotein (GP) during entry. However, the significance of cathepsin cleavage during infection remains unclear. Here we demonstrate a role for cathepsin L (CatL) cleavage of Ebola virus GP in the generation of a stable 18-kDa GP1 viral intermediate that exhibits increased binding to and infectivity for susceptible cell targets. Cell binding to a lymphocyte line was increased when CatL-proteolysed pseudovirions were used, but lymphocytes remained resistant to Ebola virus GP-mediated infection. Genetic removal of the highly glycosylated mucin domain in Ebola virus GP resulted in cell binding similar to that observed with CatL-treated full-length GP, and no overall enhancement of binding or infectivity was observed when mucin-deleted virions were treated with CatL. These results suggest that cathepsin cleavage of Ebola virus GP facilitates an interaction with a cellular receptor(s) and that removal of the mucin domain may facilitate receptor binding. The influence of CatL in Ebola virus GP receptor binding should be useful in future studies characterizing the mechanism of Ebola virus entry.

* Corresponding author. Mailing address: Department of Microbiology, University of Pennsylvania School of Medicine, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6076. Phone: (215) 573-3509. Fax: (215) 573-9068. E-mail: pbates{at}mail.med.upenn.edu

{triangledown} Published ahead of print on 10 October 2007.

{dagger} Present address: Blood Systems Research Institute, 270 Masonic Ave., San Francisco, CA 94118.

Journal of Virology, December 2007, p. 13378-13384, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01170-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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