Processing of the Borna Disease Virus Glycoprotein gp94 by the Subtilisin-Like Endoprotease Furin

Abstract

Open reading frame IV (ORF-IV) of Borna disease virus (BDV) encodes a protein with a calculated molecular mass of ca. 57 kDa (p57), which increases after N glycosylation to 94 kDa (gp94). The unglycosylated and glycosylated proteins are proteolytically cleaved by the subtilisin-like protease furin. Furin most likely recognizes one of three potential cleavage sites, namely, an arginine at position 249 of the ORF-IV gene product. The furin inhibitor decRVKRcmk decreases the production of infectious BDV significantly, indicating that proteolytic cleavage of the gp94 precursor molecule is necessary for the full biological activity of the BDV glycoprotein.

GRP78: A cell's response to stress

“…This virus infects many animals and causes central nervous system diseases which are associated with behavioral disturbances [77]. Virus entry is mediated by endocytosis after the viral envelope glycoprotein (G) attach to the cell receptor [78,79]. The N terminal in G protein is responsible for the attachment to the cell receptor [78].…”

Surface glycoprotein of Borna disease virus mediates virus spread from cell to cell

“…Correct proteolytic processing by cellular proteases is a prerequisite for the activity of many different fusogenic viral glycoproteins (Klenk and Garten, 1994;Pasquato et al, 2013), including BDV-GP (Richt et al, 1998). To verify whether the inhibition of BDV-GP cleavage prevents the fusogenic activity of GP, we analysed the fusion activity of cell surface expressed BDV-GP in the presence of MI-0701.…”

“…Aliquots of the cells were either treated or not treated with Endo H or PNGase F respectively. All samples were subjected to SDS-PAGE and immunoblotting using a BDV-GPCspecific rabbit serum that recognizes GP (94 kDa), the cleaved forms of GP-C (43 kDa) and the respective deglycosylated forms GP declyc (57 kDa) and GP-C deglyc (23 kDa) (Richt et al, 1998). The glycosylation variants of non-cleaved GP are indicated by asterisks, and the positions of GP-C forms are indicated by dots.…”

“…Cleavage of the signal peptide from pre-GP yields the immature GP, whose molecular weight is shifted to~94 kDa by extensive N-glycosylation (Schneider et al, 1997). Early during the transport along the secretory pathway from the ER to the plasma membrane, GP is further processed by the host cell protease furin (Gonzalez-Dunia et al, 1998;Richt et al, 1998;Eickmann et al, 2005). Furin is an endoprotease that preferentially cleaves its substrates at the C-terminus of the consensus sequence Arg-X-(Arg/Lys)-Arg or at the less common sequence Arg-X-X-Arg.…”

“…In addition, furin is exploited by a number of pathogens, including bacteria and many enveloped viruses, which utilize furin-mediated cleavage to activate proteins such as bacterial toxins, viral membrane proteins or fusogenic glycoproteins (Thomas, 2002). In the case of BDV, furin cleaves the GP into the distal, amino-terminal subunit GP-N (51 kDa) and the carboxy-terminal, membrane-anchored subunit of GP (GP-C) (43 kDa) (Richt et al, 1998;Kiermayer et al, 2002).…”