Inhibition of murine leukemia virus envelope protein (env) processing by intracellular expression of the env N-terminal heptad repeat region

J Virol. 2005 Apr;79(8):4782-92. doi: 10.1128/JVI.79.8.4782-4792.2005.

Abstract

A conserved structural motif in the envelope proteins of several viruses consists of an N-terminal, alpha-helical, trimerization domain and a C-terminal region that refolds during fusion to bind the N-helix trimer. Interaction between the N and C regions is believed to pull viral and target membranes together in a crucial step during membrane fusion. For several viruses with type I fusion proteins, C regions pack as alpha-helices in the grooves between N-helix monomers, and exogenously added N- and C-region peptides block fusion by inhibiting the formation of the six-helix bundle. For other viruses, including influenza virus and murine leukemia virus (MLV), there is no evidence for comparably extended C-region alpha-helices, although a short, non-alpha-helical interaction structure has been reported for influenza virus. We tested candidate N-helix and C-region peptides from MLV for their ability to inhibit cell fusion but found no inhibitory activity. In contrast, intracellular expression of the MLV N-helix inhibited fusion by efficiently blocking proteolytic processing and intracellular transport of the envelope protein. The results highlight another mechanism by which the N-helix peptides can inhibit fusion.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Fusion
  • Cell Line
  • Cricetinae
  • DNA Primers
  • Gene Products, env / chemistry
  • Gene Products, env / genetics*
  • Humans
  • Leukemia Virus, Murine / genetics*
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics*
  • Polymerase Chain Reaction
  • Repetitive Sequences, Amino Acid
  • Transfection

Substances

  • DNA Primers
  • Gene Products, env
  • Peptide Fragments