Details

Autor(en) / Beteiligte

• Kundu, Soumya
• Saadi, Fareeha
• Sengupta, Sourodip
• Antony, Gisha Rose
• Raveendran, Vineeth A.
• Kumar, Rahul
• Kamble, Mithila Ashok
• Sarkar, Lucky
• Burrows, Amy
• Pal, Debnath
• Sen, Ganes C.
• Sarma, Jayasri Das

Titel

DJ-1-Nrf2 axis is activated upon murine β-coronavirus infection in the CNS

Ist Teil von

• Brain disorders, 2021-12, Vol.4, p.100021-100021, Article 100021

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •M-CoV-induced glial cell activation in mouse brain results in activation of UPR marker XBP1 and Nrf2 mediated antioxidant responses through DJ-1. DJ-1-Nrf2 pathway is a major contributor to cellular antioxidant response to oxidative stress.•M-CoV infection in primary astrocytes and microglia results in up-regulation of DJ-1- Nrf2 antioxidant pathway and activation of XBP1.•M-CoV-induced up-regulation of DJ-1 is predicted to be under the control of its transcriptional regulator XBP1. Coronaviruses have emerged as alarming pathogens owing to their inherent ability of genetic variation and cross-species transmission. Coronavirus infection burdens the endoplasmic reticulum (ER.), causes reactive oxygen species production and induces host stress responses, including unfolded protein response (UPR) and antioxidant system. In this study, we have employed a neurotropic murine β-coronavirus (M-CoV) infection in the Central Nervous System (CNS) of experimental mice model to study the role of host stress responses mediated by interplay of DJ-1 and XBP1. DJ-1 is an antioxidant molecule with established functions in neurodegeneration. However, its regulation in virus-induced cellular stress response is less explored. Our study showed that M-CoV infection activated the glial cells and induced antioxidant and UPR genes during the acute stage when the viral titer peaks. As the virus particles decreased and acute neuroinflammation diminished at day ten p.i., a significant up-regulation in UPR responsive XBP1, antioxidant DJ-1, and downstream signaling molecules, including Nrf2, was recorded in the brain tissues. Additionally, preliminary in silico analysis of the binding between the DJ-1 promoter and a positively charged groove of XBP1 is also investigated, thus hinting at a mechanism behind the upregulation of DJ-1 during MHV-infection. The current study thus attempts to elucidate a novel interplay between the antioxidant system and UPR in the outcome of coronavirus infection.