Long Non-Coding RNAs in Viral Infection

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08803
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Hokkaido University
• Principal Investigator: Carr Michael 北海道大学, 国際連携研究教育局, 准教授 (70769588)
• Research Collaborator: Sawa Hirofumi
• Project Period (FY): 2016-10-21 – 2019-03-31
• Keywords: Flavivirus / RNA-seq / transcriptomics / JEV / Zika virus / SH-SY5Y / neuron / Endoplasmic reticulum

Outline of Final Research Achievements

We made publicly available the first JEV-infected neuronal transcriptome for research on flavivirus-associated neuropathology. We focused on previously unrecognised responses to virus infection: upregulation of novel ER stress signalling transcripts (Sestrin2 and TRIB3) and of the light and heavy chains of the xCT amino acid antiporter. The prior link between elevated SESN2 and Parkinson’s disease is intriguing in the context of JEV infection as one of the distinct neurological sequelae associated with JEV is a Parkinsonian-like phenotype. SESN2 levels in brains of flavivirus models should be examined. Our findings raise the possibility that xCT activation and efflux of the amino acid glutamate (activator of excitatory neurotransmitter receptors) is potentially implicated in the pathophysiology of JEV-induced neurodegeneration. Perturbation of xCT by drugs in vivo should be performed to see the impact on viral replication and survival rates in mouse models of flavivirus encephalitis.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

The academic significance rests on a publicly available database of a JEV-infected neuronal transcriptome for researchers studying flavivirus-induced neuropathogenesis. The social significance derives from allowing a deepening of collaboration between scientists in Japan with colleagues overseas.