title: Nonstructural Protein 1 of Tick-Borne Encephalitis Virus Induces Oxidative Stress and Activates Antioxidant Defense by the Nrf2/ARE Pathway.
abstract: BACKGROUND
  Infection with tick-borne encephalitis virus (TBEV) causes pathological changes in the central nervous system. However, the possible redox alterations in the infected cells that can contribute to the virus pathogenicity remain unknown.
  
  
  OBJECTIVE
  In the current study we explored the ability of TBEV nonstructural protein 1 (NS1) to induce oxidative stress and activate antioxidant defense via the nuclear factor (erythroid-derived-2)-like 2/antioxidant response element (Nrf2/ARE) pathway.
  
  
  METHODS
  HEK 293T cells were transfected with plasmid encoding NS1 protein, and the production of reactive oxygen species (ROS) was measured using oxidation-sensitive dyes, the activation of the ARE promoter was estimated using a reporter plasmid, and the expression of phase II detoxifying enzymes was quantified by measuring their mRNA levels using RT-qPCR.
  
  
  RESULTS
  A high level of ROS production was detected in cells transfected with NS1-expressing plasmid. In addition, this protein activated the promoter with an ARE and upregulated the transcription of ARE-dependent genes that encode phase II enzymes.
  
  
  CONCLUSIONS
  TBEV NS1 protein both triggers ROS production and activates a defense Nrf2/ARE pathway. These data suggest that a role of redox-mediated processes in TBEV-induced damage of the central nervous system should also be explored. These data can contribute to a better understanding of TBEV pathogenicity, further improvement of TBE treatment, and the development of vaccine candidates against this infection.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Kuzmenko
authors.forename: Olga A
authors.initials: OA
authors.lastname: Smirnova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ivanov
authors.forename: Elizaveta S
authors.initials: ES
authors.lastname: Starodubova
authors.forename: Vadim L
authors.initials: VL
authors.lastname: Karpov
mesh_terms: D061745:Antioxidant Response Elements; D004669:Encephalitis Viruses, Tick-Borne / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D017361:Viral Nonstructural Proteins