Nonstructural Protein 1 of Tick-Borne Encephalitis Virus Induces Oxidative Stress and Activates Antioxidant Defense by the Nrf2/ARE Pathway

作者：Kuzmenko Yulia V; Smirnova Olga A; Ivanov Alexander V; Starodubova Elizaveta S; Karpov Vadim L

来源：Intervirology, 2016, 59(2): 111-117.

DOI：10.1159/000452160

<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; 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. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; 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. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; 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. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; 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. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; 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.</jats:p>

• 出版日期2016