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• W2112851172 endingPage "12720" @default.
• W2112851172 startingPage "12714" @default.
• W2112851172 abstract "ABSTRACT Proteolytic processing of paramyxovirus fusion (F) proteins is essential for the generation of a mature and fusogenic form of the F protein. Although many paramyxovirus F proteins are proteolytically processed by the cellular protease furin at a multibasic cleavage motif, cleavage of the newly emerged Hendra virus F protein occurs by a previously unidentified cellular protease following a single lysine at residue 109. We demonstrate here that the cellular protease cathepsin L is involved in converting the Hendra virus precursor F protein (F 0 ) to the active F 1 + F 2 disulfide-linked heterodimer. To initially identify the class of protease involved in Hendra virus F protein cleavage, Vero cells transfected with pCAGGS-Hendra F or pCAGGS-SV5 F (known to be proteolytically processed by furin) were metabolically labeled and chased in the absence or presence of serine, cysteine, aspartyl, and metalloprotease inhibitors. Nonspecific and specific protease inhibitors known to decrease cathepsin activity inhibited proteolytic processing of Hendra virus F but had no effect on simian virus 5 F processing. We next designed shRNA oligonucleotides to cathepsin L which dramatically reduced cathepsin L protein expression and enzyme activity. Cathepsin L shRNA-expressing Vero cells transfected with pCAGGS-Hendra F demonstrated a nondetectable amount of cleavage of the Hendra virus F protein and significantly decreased membrane fusion activity. Additionally, we found that purified human cathepsin L processed immunopurified Hendra virus F 0 into F 1 and F 2 fragments. These studies introduce a novel mechanism for primary proteolytic processing of viral glycoproteins and also suggest a previously unreported biological role for cathepsin L." @default.
• W2112851172 created "2016-06-24" @default.
• W2112851172 creator A5045661242 @default.
• W2112851172 creator A5051559566 @default.
• W2112851172 date "2005-10-15" @default.
• W2112851172 modified "2023-10-16" @default.
• W2112851172 title "Cathepsin L Is Involved in Proteolytic Processing of the Hendra Virus Fusion Protein" @default.
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• W2112851172 doi "https://doi.org/10.1128/jvi.79.20.12714-12720.2005" @default.
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