Alpha-synuclein expression in neurons modulates Japanese encephalitis virus infection.

Autor:	Gupta A; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India., Bohara VS; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India., Chauhan AS; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India., Mohapatra A; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India., Kaur H; Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research, Ansari Nagar, New Delhi, India., Sharma A; Department of Microbiology, Gauhati Medical College, Guwahati, Assam, India., Chaudhary N; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India., Kumar S; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2024 Dec 17; Vol. 98 (12), pp. e0041824. Date of Electronic Publication: 2024 Nov 07.
DOI:	10.1128/jvi.00418-24
Abstrakt:	Japanese encephalitis virus (JEV) stands as a prominent vector-borne zoonotic pathogen, displaying neurotropism and eliciting Parkinson's disease (PD)-like symptoms among most symptomatic survivors. A characteristic feature of PD is the aggregation of mutated α-synuclein (α-syn) that damages the dopaminergic neurons. Considering this link between JEV-induced PD-like symptoms and α-syn pathogenesis, we explored the role of α-syn in JEV infectivity in neuronal cells. Our investigation revealed a significant increase in endogenous α-syn expression in JEV-infected cells. In addition, exogenous α-syn (Exoα-syn) treatment substantially reduced JEV replication, suggesting its anti-JEV effect. Furthermore, Exoα-syn treatment led to the upregulation of superoxide dismutase 1 (SOD1) and reduction in reactive oxygen species (ROS). The results were validated by endogenous α-syn-silencing, which decreased SOD1 and raised ROS levels in neuronal cells. Similarly, the SOD1 inhibition via LCS-1 also intensified ROS and JEV infection. Silencing of SOD1 in α-syn overexpressing neuro2a cells exhibited increased JEV replication. Overall, our results suggest that α-syn exerts an anti-JEV effect by regulating protein involved in oxidative stress inside neuronal cells. This study contributes valuable insights into the interplay between α-syn expression and JEV infectivity, shedding light on avenues further to investigate the potential role of α-syn in JEV pathogenesis. Importance: Japanese encephalitis virus (JEV) poses a significant threat, particularly to children. Despite extensive research efforts, the development of effective treatments against JEV has been impeded. One of the major setbacks is a lack of comprehensive understanding of neurotropism. The study focuses on alpha-synuclein (α-syn), a neuronal protein, and aims to determine its role in JEV pathogenesis. The present study reveals that the host cell upregulates α-syn in response to JEV infection. α-syn restrains JEV propagation by modulating superoxide dismutase 1 (SOD1) expression which further blocks JEV-induced ROS generation. Endogenous α-syn silencing led to a decrease in SOD1 expression and increased viral titer. α-syn plays a crucial role in counteracting oxidative stress through SOD1, which is essential for limiting JEV replication. This study provides broader implications for antiviral strategies and their possible role in neurodegenerative diseases; however, there is still much to explore, particularly regarding α-syn aggregation kinetics in JEV infection. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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