2018 Fiscal Year Final Research Report

Pathogenesis of rotavirus antigenemia and extraintestinal manifestations

Research Project

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Project/Area Number	15K08628
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Laboratory medicine
Research Institution	Fujita Health University
Principal Investigator	Sugata Ken 藤田医科大学, 医学部, 講師 (60454401)
Co-Investigator(Kenkyū-buntansha)	井平勝藤田医科大学, 保健学研究科, 教授 (10290165) 三浦浩樹藤田医科大学, 医学部, 助教 (10751761) 工藤寿子藤田医科大学, 医学部, 准教授 (20303620) 吉川哲史藤田医科大学, 医学部, 教授 (80288472)
Project Period (FY)	2015-04-01 – 2019-03-31
Keywords	ロタウイルス（RV) / 抗原血症 / C群ロタウイルス（GCRV) / 型特異リアルタイムRT-PCR / RV5(５価ロタウイルスワクチン） / X-SCID / リアソートメント / リアソータント
Outline of Final Research Achievements	1.28 children hospitalized for treatment of malignant diseases during the RV outbreak were enrolled in this study. 14 patients developed RVGE during the period.RV antigenemia was detected in 22 of the 28 patients.Mean age of the patients was significantly lower in RVGE than non RVGE group.2.30 hospitalized children with acute GE were enrolled for the diagnosis of GARV and GCRV.6 were positive for GCRV by ELISA, RT-PCR and electron microscopy, whereas 16 were positive for GARV.Hepatitis were not seen in GCRV group.3.7‐month‐old boy diagnosed with X‐linked SCID demonstrated chronic GE following the 3rd administration of RV5 and failure to thrive.High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples. NGS analysis revealed genetic reassortment in the VP7 gene and the VP4 gene among vaccine strains. In addition,PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis.
Free Research Field	小児感染症ウイルス
Academic Significance and Societal Importance of the Research Achievements	我々の開発した型特異リアルタイムRT-PCR法は、ワクチン接種後の5種類の異なる遺伝子型の生体内増殖モニタリングに有用である。この手法を用い乳児院におけるRVワクチン接種後乳児のRVワクチン株の便排泄状況をモニタリングし、周囲における伝播のないことを報告した。腸管外合併症のある患者がワクチン接種後である場合にはどのような遺伝子型による合併症であるのか、または変異がみとめられているのかあるいはRNA血症もみとめているのかなどこれらが解明できればウイルス学的な意義は大変に大きく、ワクチン防御効果の検討だけではなく、次世代のワクチン開発においても貢献度は計り知れない。