A highly membrane-active peptide in Flock House virus: implications for the mechanism of nodavirus infection

Chem Biol. 1999 Jul;6(7):473-81. doi: 10.1016/s1074-5521(99)80065-9.


Background: Nodaviruses are among the simplest animal viruses, and are therefore attractive systems for deconvoluting core viral processes such as assembly, infection and uncoating. Membrane translocation of the single-stranded RNA genome of nodaviruses has been proposed to be mediated by direct lipid-protein interactions between a post-assembly autocatalytic cleavage product from the capsomere and the target membrane. To probe the validity of this hypothesis, we have synthesized a 21-residue Met-->Nle (norleucine) variant of the amino-terminal helical domain (denoted here as gamma1) of the cleavage peptide in Flock House nodavirus (FHV) and studied its ability to alter membrane structure and function.

Results: The synthetic peptide gamma1 increases membrane permeability to hydrophilic solutes, as judged by fluorescence experiments with liposome-encapsulated dyes and ion-conductance measurements. Furthermore, peptide orientation and location within lipid bilayers was determined using tryptophan-fluorescence-quenching experiments and attenuated total reflectance infrared spectroscopy.

Conclusions: The helical domain of the FHV cleavage product partitions spontaneously into lipid bilayers and increases membrane permeability, consistent with the postulated mechanism for viral genome translocation. The existence of a membrane-binding domain in the FHV cleavage sequence suggests peptide-triggered disruption of the endosomal membrane as a prelude to viral uncoating in the host cytoplasm. A model for this interaction is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Capsid / chemistry*
  • Insect Viruses / genetics
  • Insect Viruses / pathogenicity*
  • Liposomes
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • RNA Viruses / genetics
  • RNA Viruses / pathogenicity*
  • Spectrometry, Fluorescence
  • Spectroscopy, Fourier Transform Infrared
  • Viral Proteins / chemistry*
  • Viral Proteins / genetics
  • Virus Assembly


  • Liposomes
  • Viral Proteins