Bunyamwera orthobunyavirus glycoprotein precursor is processed by cellular signal peptidase and signal peptide peptidase

Abstract

The M genome segment of Bunyamwera virus (BUNV)-The prototype of both theBunyaviridaefamily and theOrthobunyavirus genus-encodes the glycoprotein precursor (GPC) that is proteolytically cleaved to yield two viral structural glycoproteins, Gn and Gc, and a nonstructural protein, NSm. The cleavage mechanism of orthobunyavirus GPCs and the host proteases involved have not been clarified. In this study, we investigated the processing of BUNV GPC and found that both NSm and Gc proteins were cleaved at their own nternal signal peptides (SPs), in which NSm domain I functions as P Sm nd NSm domain V as SP c Moreover, the domain I was further rocessed by a host intramembrane-cleaving protease, signal peptide eptidase, and is required for cellfusion activities. Meanwhile, the Sm domain V (SP c remains integral to NSm, rendering the NSm opology as a two-membrane-spanning integral membrane protein. e defined the cleavage sites and boundaries between the processed roteins as follows: Gn, from residue 17-312 or nearby residues; NSm, 32-477; and Gc, 478-1433. Our data clarified the mechanism of the recursor cleavage process, which is important for our understanding f viral glycoprotein biogenesis in the genusOrthobunyavirusand hus presents a useful target for intervention strategies.