Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells

Daniel Ebert, Jan Deussing, Christoph Peters, Terence S. Dermody

Research output: Contribution to journalArticle

Abstract

After attachment to receptors, reovirus virions are internalized by endocytosis and exposed to acid-dependent proteases that catalyze viral disassembly. Previous studies using the cysteine protease inhibitor E64 and a mutant cell line that does not support reovirus disassembly suggest a requirement for specific endocytic proteases in reovirus entry. This study identifies the endocytic proteases that mediate reovirus disassembly in murine fibroblast cells. Infection of both L929 cells treated with the cathepsin L inhibitor Z-Phe-Tyr(tBu)-diazomethyl ketone and cathepsin L-deficient mouse embryo fibroblasts resulted in inefficient proteolytic disassembly of viral outer-capsid proteins and decreased viral yields. In contrast, both L929 cells treated with the cathepsin B inhibitor CA-074Me and cathepsin B-deficient mouse embryo fibroblasts support reovirus disassembly and growth. However, removal of both cathepsin B and cathepsin L activity completely abrogates disassembly and growth of reovirus. Concordantly, cathepsin L mediates reovirus disassembly more efficiently than cathepsin B in vitro. These results demonstrate that either cathepsin L or cathepsin B is required for reovirus entry into murine fibroblasts and indicate that cathepsin L is the primary mediator of reovirus disassembly. Moreover, these findings suggest that specific endocytic proteases can determine host cell susceptibility to infection by intracellular pathogens.

Original languageEnglish (US)
Pages (from-to)24609-24617
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number27
DOIs
StatePublished - Jul 5 2002
Externally publishedYes

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Cathepsin L
Cathepsin B
Fibroblasts
Cells
Peptide Hydrolases
Embryonic Structures
Cysteine Proteinase Inhibitors
Capsid Proteins
Pathogens
Growth
Endocytosis
Infection
Virion
Cell Line
Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells. / Ebert, Daniel; Deussing, Jan; Peters, Christoph; Dermody, Terence S.

In: Journal of Biological Chemistry, Vol. 277, No. 27, 05.07.2002, p. 24609-24617.

Research output: Contribution to journalArticle

Ebert, Daniel ; Deussing, Jan ; Peters, Christoph ; Dermody, Terence S. / Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 27. pp. 24609-24617.
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