title: Entry functions and antigenic structure of flavivirus envelope proteins.
abstract: The envelope proteins (E) of flaviviruses form an icosahedral cage-like structure of homodimers that cover completely the surface of mature virions and are responsible for receptor-binding and membrane fusion. Fusion is triggered by the acidic pH in endosomes which induces dramatic conformational changes of E that drive the merger of the membranes. We have identified an alternative trigger that induces the first phase of the fusion process only, but then leads to an arrest at an intermediate stage. These data suggest that the early and late stages of flavivirus fusion are differentially controlled by intersubunit and intrasubunit constraints of the fusion protein, respectively. Details of the molecular antigenic structure of the flavivirus E protein were revealed by the use of neutralization escape mutants as well as recombinant expression systems for the generation of virus-like particles. The experimental data provide evidence that each of the three domains contributing to the external face of the E protein can induce and bind neutralizing antibodies. Broadly flavivirus cross-reactive antibodies, however, primarily recognize a site involving residues of the highly conserved fusion peptide loop which is cryptic and largely inaccessible on the surface of native infectious virions.
authors.affiliation: Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A1095 Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Stiasny
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiermayr
authors.forename: Franz X
authors.initials: FX
authors.lastname: Heinz
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology*; D018177:Flavivirus Infections / Q000276:immunology; D006801:Humans; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*; D014771:Virion / Q000737:chemistry / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D014759:Viral Envelope Proteins