Role of N-glycan trimming in the folding and secretion of the pestivirus protein Erns

N-glycosylation inhibitors have antiviral effect against bovine viral diarrhea virus. This effect is associated with inhibition of the productive folding pathway of E1 and E2 envelope glycoproteins. E-rns is the third pestivirus envelope protein, essential for virus infectivity. The protein is heavily glycosylated, its N-linked glycans counting for half of the apparent molecular weight. In this report we address the importance of N-glycan trimming in the biosynthesis, folding, and intracellular trafficking of E-rns. We show that E-rns folding is not assisted by calnexin and calreticulin; however, the protein strongly interacts with BiP. Consistently, the N-glycan trimming is not a prerequisite for either the acquirement of the E-rns native conformation, as it retains the RNase enzymatic activity in the presence of alpha-glucosidase inhibitors, or for dimerization. However, E-rns secretion into the medium is severely impaired suggesting a role for N-glycosylation in the transport of the glycoprotein through the secretory pathway. (C) 2004 Elsevier Inc. All rights reserved.