title: Evidence of a humoral response to a novel protein WARF4 embedded in the West Nile virus NS4B gene encoded by an alternative open reading frame.
abstract: West Nile virus (WNV) is a flavivirus that is maintained in a bird-mosquito transmission cycle. Humans, horses and other non-avian vertebrates are usually incidental hosts. However, WNV is a neurotropic virus, which requires an efficient humoral response for the control of a neuroinvasive infection. The WNV genome encodes three structural (capsid, premembrane/membrane and envelope) and seven non-structural proteins. Bioinformatic analysis performed on the WNV genomes detected a conserved alternative open reading frame restricted to the lineage I virus. To quickly verify the existence of this putative protein, entitled West Nile Alternative Reading Frame 4 (WARF4), we produced a prokaryotic recombinant source of WARF4 and verified its immunogenicity in vivo by analyzing 43 horse serum samples, of which 15 were positive for antibodies to WNV premembrane and envelope (prM-E) proteins. Specific antibodies to WARF4 were significantly detected in 5 out of the 15 serum samples testing positive for antibodies to prM-E WNV proteins. Our findings provide evidence of a significant antibody response to the WARF4 protein in the serum of the horse testing positive for antibodies to prM-E proteins, thus indicating that this antigen might be a potential tool for further characterization of the immune response of WNV infections in humans as well.
authors.affiliation: Laboratory of Molecular Biology, Army Medical Research Centre, I-00184 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Faggioni
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciammaruconi
authors.forename: Riccardo
authors.initials: R
authors.lastname: De Santis
authors.forename: Alice
authors.initials: A
authors.lastname: Pomponi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scicluna
authors.forename: Katia
authors.initials: K
authors.lastname: Barbaro
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Autorino
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
authors.forename: Florigio
authors.initials: F
authors.lastname: Lista
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D019295:Computational Biology / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D016679:Genome, Viral; D006734:Horse Diseases / Q000097:blood / Q000821:virology; D006736:Horses; D007106:Immune Sera / Q000276:immunology; D016366:Open Reading Frames / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007106:Immune Sera; C080107:NS4B protein, flavivirus; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C542426:WARF4 protein, West Nile virus