title: A highly membrane-active peptide in Flock House virus: implications for the mechanism of nodavirus infection.
abstract: 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.
authors.affiliation: Departments of Chemistry and Molecular Biology at the Scripps Research Institute, Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Bong
authors.forename: C
authors.initials: C
authors.lastname: Steinem
authors.forename: A
authors.initials: A
authors.lastname: Janshoff
authors.forename: J E
authors.initials: JE
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Reza Ghadiri
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002213:Capsid / Q000737:chemistry*; D007304:Insect Viruses / Q000235:genetics / Q000472:pathogenicity*; D008081:Liposomes; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D012328:RNA Viruses / Q000235:genetics / Q000472:pathogenicity*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics; D019065:Virus Assembly
chemical_list: D008081:Liposomes; D014764:Viral Proteins