title: Intracellular degradation and localization of NS1 of tick-borne encephalitis virus affect its protective properties.
abstract: Currently, many DNA vaccines against infectious diseases are in clinical trials; however, their efficacy needs to be improved. The potency of DNA immunogen can be optimized by targeting technologies. In the current study, to increase the efficacy of NS1 encoded by plasmid, proteasome targeting was applied. NS1 variants with or without translocation sequence and with ornithine decarboxylase as a signal of proteasomal degradation were tested for expression, localization, protein turnover, proteasomal degradation and protection properties. Deletion of translocation signal abrogated presentation of NS1 on the cell surface and increased proteasomal processing of NS1. Fusion with ornithine decarboxylase led to an increase of protein turnover and the proteasome degradation rate of NS1. Immunization with NS1 variants with increased proteasome processing protected mice from viral challenge only partially; however, the survival time of infected mice was prolonged in these groups. These data can give a presupposition for formulation of specific immune therapy for infected individuals.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Kuzmenko
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Elizaveta S
authors.initials: ES
authors.lastname: Starodubova
authors.affiliation: Chumakov Institute of Poliomyelitis and Viral Encephalitides (Chumakov IPVE), Chumakov FSC R&D IBP RAS, Moscow, Russia.
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Shevtsova
authors.affiliation: Chumakov Institute of Poliomyelitis and Viral Encephalitides (Chumakov IPVE), Chumakov FSC R&D IBP RAS, Moscow, Russia.
authors.forename: Liubov L
authors.initials: LL
authors.lastname: Chernokhaeva
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Latanova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Preobrazhenskaia
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Timofeev
authors.affiliation: Chumakov Institute of Poliomyelitis and Viral Encephalitides (Chumakov IPVE), Chumakov FSC R&D IBP RAS, Moscow, Russia.
authors.forename: Galina G
authors.initials: GG
authors.lastname: Karganova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Vadim L
authors.initials: VL
authors.lastname: Karpov
mesh_terms: D000818:Animals; D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology*; D051379:Mice; D059748:Proteolysis; D016019:Survival Analysis; D017361:Viral Nonstructural Proteins / Q000276:immunology* / Q000378:metabolism*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines