title: Inhibition of hendra virus fusion.
abstract: Hendra virus (HeV) is a recently identified paramyxovirus that is fatal in humans and could be used as an agent of bioterrorism. The HeV receptor-binding protein (G) is required in order for the fusion protein (F) to mediate fusion, and analysis of the triggering/activation of HeV F by G should lead to strategies for interfering with this key step in viral entry. HeV F, once triggered by the receptor-bound G, by analogy with other paramyxovirus F proteins, undergoes multistep conformational changes leading to a six-helix bundle (6HB) structure that accomplishes fusion of the viral and cellular membranes. The ectodomain of paramyxovirus F proteins contains two conserved heptad repeat regions (HRN and HRC) near the fusion peptide and the transmembrane domains, respectively. Peptides derived from the HRN and HRC regions of F are proposed to inhibit fusion by preventing F, after the initial triggering step, from forming the 6HB structure that is required for fusion. HeV peptides have previously been found to be effective at inhibiting HeV fusion. However, we found that a human parainfluenza virus 3 F-peptide is more effective at inhibiting HeV fusion than the comparable HeV-derived peptide.
authors.affiliation: Department of Pediatrics, Weill Medical College of Cornell University, 515 E. 71st St., 6th Floor, New York, NY 10021, USA.
authors.forename: M
authors.initials: M
authors.lastname: Porotto
authors.forename: L
authors.initials: L
authors.lastname: Doctor
authors.forename: P
authors.initials: P
authors.lastname: Carta
authors.forename: M
authors.initials: M
authors.lastname: Fornabaio
authors.forename: O
authors.initials: O
authors.lastname: Greengard
authors.forename: G E
authors.initials: GE
authors.lastname: Kellogg
authors.forename: A
authors.initials: A
authors.lastname: Moscona
mesh_terms: D000595:Amino Acid Sequence; D002459:Cell Fusion; D002460:Cell Line; D045404:Hendra Virus / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D014760:Viral Fusion Proteins