Role of N-glycan trimming in the folding and secretion of the pestivirus protein E(rns)

Biochem Biophys Res Commun. 2004 Jun 25;319(2):655-62. doi: 10.1016/j.bbrc.2004.05.039.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Dimerization
  • Glycosylation
  • Membrane Glycoproteins / metabolism*
  • Molecular Chaperones / metabolism
  • Polysaccharides / metabolism*
  • Protein Folding*
  • Viral Envelope Proteins / metabolism*

Substances

  • E(rns) protein, classic swine fever virus
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Polysaccharides
  • Viral Envelope Proteins