Cathepsin L Is Involved in Proteolytic Processing of the Hendra Virus Fusion Protein

• DOI: 10.1128/jvi.79.20.12714-12720.2005
• Publication Date: 2005-09-27T15:57:38Z
• Authors: Cara Theresia Pager; Rebecca Ellis Dutch
• Keywords: Cathepsin L; Furin; Cathepsin E; Hendra Virus; NS3; Cathepsin L1

Proteolytic processing of paramyxovirus fusion (F) proteins is essential for the generation a mature and fusogenic form F protein. Although many are proteolytically processed by cellular protease furin at multibasic cleavage motif, newly emerged Hendra virus protein occurs previously unidentified following single lysine residue 109. We demonstrate here that cathepsin L involved in converting precursor (F(0)) to active F(1) + F(2) disulfide-linked heterodimer. To initially identify class cleavage, Vero cells transfected with pCAGGS-Hendra or pCAGGS-SV5 (known be furin) were metabolically labeled chased absence presence serine, cysteine, aspartyl, metalloprotease inhibitors. Nonspecific specific inhibitors known decrease activity inhibited proteolytic but had no effect on simian 5 processing. next designed shRNA oligonucleotides which dramatically reduced expression enzyme activity. Cathepsin shRNA-expressing demonstrated nondetectable amount significantly decreased membrane Additionally, we found purified human immunopurified F(0) into fragments. These studies introduce novel mechanism primary viral glycoproteins also suggest unreported biological role L.