Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide.
Unlike other class I viral fusion proteins, spike proteins on severe acute respiratory syndrome coronavirus virions are uncleaved. As we and others have demonstrated, infection by this virus depends on cathepsin proteases present in endosomal compartments of the target cell, suggesting that the spike protein acquires its fusion competence by cleavage during cell entry rather than during virion biogenesis. Here we demonstrate that cathepsin L indeed activates the membrane fusion function of the spike protein. Moreover, cleavage was mapped to the same region where, in coronaviruses carrying furin-activated spikes, the receptor binding subunit of the protein is separated from the membrane-anchored fusion subunit.
Bosch
Berend Jan
BJ
Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Institute of Biomembranes, Utrecht, The Netherlands.
Bartelink
Willem
W
Rottier
Peter J M
PJ
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000378:metabolism; D010957:Plasmids; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000145:classification* / Q000378:metabolism*
D010455:Peptides; D014760:Viral Fusion Proteins; D049452:Green Fluorescent Proteins; D002403:Cathepsins; D014357:Trypsin; D003546:Cysteine Endopeptidases; D056668:Cathepsin L