2020 Fiscal Year Final Research Report

Reverse genetics system for Ibaraki virus reveals the pathogenecity of double-stranded RNA virus

Research Project

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Project/Area Number	18K05992
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 42020:Veterinary medical science-related
Research Institution	Kobe University
Principal Investigator	Matsuo Eiko 神戸大学, 農学研究科, 助教 (40620878)
Co-Investigator(Kenkyū-buntansha)	万谷洋平神戸大学, 農学研究科, 助教 (30724984)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	二本鎖RNAウイルス / リアソータント / ウイルス複製 / 感染動態
Outline of Final Research Achievements	Ibaraki virus (IBAV) is a member of the epizootic hemorrhagic disease virus (EHDV) serogroup, which belongs to the Orbivirus genus of the Reoviridae family. Although EHDV infection in cattle is subclinical in most cases, EHDV is still an ongoing threat to livestock in the world. Recently we developed reverse genetics system for IBAV, to clarify the molecular mechanism of orbivirus replication. Here, we produced a series of reassortant EHDV to evaluate which segments are most critical for the pathogenicity. It was revealed that EHDV-6 genes affected virus production. In addition, using reassortant EHDV, we screened bloods collected from Japanese Black for the infection of EHDV. Together with previous studies, we demonstrated that the suppression of IBAV protein translation in the several cell lines was likely due to a misformation of translation initiation complex at 5' end of IBAV mRNA. Further, we tried to analyze how IBAV gene expression affects host-factor dynamics.
Free Research Field	分子ウイルス学
Academic Significance and Societal Importance of the Research Achievements	IBAVをはじめとするdsRNAウイルスは、複製機構が特殊性であり、一部のウイルス以外はヒトに致死的な影響を及ぼすことが少ないため、ヘルペスウイルスや、インフルエンザウイルス、肝炎ウイルスなどのウイルスに比べて疫学以外の研究があまり進んでいない。特に、「何故病気を引き起こすのか」という病原ウイルス研究の根本的な謎についてはほとんど手つかずのままである。本研究により得られた様々な知見や実験手法は、今後ウイルス学だけでなく、様々な分野での応用が期待できるだけでなく、現在は補液などの対症療法しかないイバラキ病や他のdsRNAウイルス感染症に対する新規治療法の開発など、幅広い応用が期待される。