Proteolysis of the Ebola virus glycoproteins enhances virus binding and infectivity.
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.
Kaletsky
Rachel L
RL
Department of Microbiology, University of Pennsylvania School of Medicine, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.
Simmons
Graham
G
Bates
Paul
P
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D029043:Ebolavirus / Q000378:metabolism* / Q000472:pathogenicity* / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells / Q000821:virology; D009077:Mucins / Q000235:genetics; D011480:Protease Inhibitors / Q000494:pharmacology; D014709:Vero Cells / Q000821:virology; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology; D053585:Virus Attachment / Q000187:drug effects*
D006023:Glycoproteins; D009077:Mucins; D011480:Protease Inhibitors; D014759:Viral Envelope Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L