title: Validation of a structural comparison of the antigenic characteristics of Usutu virus and West Nile virus envelope proteins.
abstract: Cross-reactions observed in serological assays between Usutu virus (USUV), the USUV outlier subtype strain CAR_1969 and West Nile virus (WNV) suggest that they share antigenic features amongst their structural outer proteins especially envelope (E) proteins. To investigate the molecular background of this observation, we compared the E protein sequences of seven USUV strains, USUV subtype strain CAR_1969 and WNV strain 2471, focusing on the binding site defined by the WNV neutralizing antibody E16. USUV SouthAfrica_1959 differs from WNV 2741 in three of four residues critical for E16 antibody binding and five of the 12 additionally involved residues. In contrast, USUV subtype CAR_1969 differs from WNV 2741 in two critical residues and five additional residues. Furthermore, USUV subtype CAR_1969 differs from other USUV strains in two critical residues. E16 antibody binding has previously been shown to be highly specific for WNV; thus, the observed variation in amino acid residues suggests that the region corresponding to the WNV E16 epitope is probably not responsible for the observed cross-reactions between WNV and USUV. Seroneutralisation assays confirmed these findings for WNV and USUV, however, showed occurring cross-reactivity between WNV and USUV subtype CAR_1969 at high antibody titers. The sequence diversity in this region might also explain some of the observed different antigenic characteristics of USUV strains and USUV subtype CAR_1969. A therapeutic effect of E16 antibody has been described in WNV infected mice; therefore, a USUV specific antibody generated against the region corresponding to the WNV E16 binding site might represent an approach for treating USUV infections.
authors.affiliation: Unité des arbovirus et virus de fièvres hémorragiques, Institut Pasteur de Dakar, 36 Avenue Pasteur, BP 220 Dakar, Senegal; Faculty of Life Sciences, University of Vienna, Dr. Bohr-Gasse 9/3, A-1030 Vienna, Austria; Faculté de Médecine, Pharmacie, Odonto-stomatologie, Université Cheikh Anta Diop Dakar, 24 Avenue Cheikh Anta Diop, Dakar, Senegal. Electronic address: birgitnikolay@gmail.com.
authors.forename: Birgit
authors.initials: B
authors.lastname: Nikolay
authors.affiliation: Unité des arbovirus et virus de fièvres hémorragiques, Institut Pasteur de Dakar, 36 Avenue Pasteur, BP 220 Dakar, Senegal. Electronic address: gfdrame@pasteur.sn.
authors.forename: Gamou
authors.initials: G
authors.lastname: Fall
authors.affiliation: Faculté de Médecine, Pharmacie, Odonto-stomatologie, Université Cheikh Anta Diop Dakar, 24 Avenue Cheikh Anta Diop, Dakar, Senegal. Electronic address: cheikh.boye@ucad.edu.sn.
authors.forename: Cheikh Saad Bouh
authors.initials: CS
authors.lastname: Boye
authors.affiliation: Unité des arbovirus et virus de fièvres hémorragiques, Institut Pasteur de Dakar, 36 Avenue Pasteur, BP 220 Dakar, Senegal. Electronic address: asall@pasteur.sn.
authors.forename: Amadou Alpha
authors.initials: AA
authors.lastname: Sall
authors.affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Dr. Bohr-Gasse 9/3, A-1030 Vienna, Austria. Electronic address: timothy.skern@meduniwien.ac.at.
authors.forename: Tim
authors.initials: T
authors.lastname: Skern
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology*; D003429:Cross Reactions; D018349:Encephalitis Viruses, Japanese / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D017385:Sequence Homology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D014759:Viral Envelope Proteins
keywords: Antigenic cross-reaction; E16 antibody; Envelope protein; Usutu virus; West Nile virus