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• Clinical and virological impacts of human parvovirus B19 epidemics on fulminant myocarditis in childhood.

  Motomura Y, Takemoto R, Yamamura K, Nagata H, Miyata T, Yoshizato R, Kaku N, Ihara K, Imadome KI, Ohno S, Ohga S

  BMC pediatrics   26 ( 1 ) 127 - 127   2026.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

  　View Summary

  BACKGROUND: Outbreaks of pediatric myocarditis and increased activity of human parvovirus B19 (B19V) have been reported worldwide following the coronavirus disease 2019 (COVID-19) pandemic. However, the direct association between prevalent erythema infectiosum and fulminant myocarditis (FM) remains elusive because of the lack of surveillance data. This study aimed to evaluate the incidence of pediatric FM during the prolonged period and to characterize B19V genotypes and clinical outcomes of the positive cases for improved disease control. METHODS: Pediatric patients with FM retrospectively underwent clinical and comprehensive virological analyses at one of the largest tertiary centers in Japan from 2009 to 2024, encompassing three epidemic periods of erythema infectiosum. The incidence of FM with and without B19V infection was analyzed using a Poisson regression model. Clinical and laboratory findings were compared between B19V-positive and B19V-negative patients. Genotypic variations of the isolated B19V strains were also examined. RESULTS: Twenty-one (median age: 5 years, range: 1 month–14 years) of 33 patients underwent viral study. Eight (38%) patients were positive for B19V DNA (1.15–6.11 log10 copies/ml). The incidence of B19V-positive FM in the three epidemic periods was significantly greater than that in the other study periods (1.33/year vs. 0.26/year, incidence rate ratio: 5.1 [1.2–21], p = 0.03). The youngest B19V-positive patient was a 4-month-old infant with a sufficient B19V-specific IgG level at presentation. B19V-specific IgM levels were positively correlated with the viral loads under the cutoff diagnostic index for erythema infectiosum (correlation coefficient: 0.970, p = 0.0005). B19V-positive patients showed higher cardiac enzyme levels, lower ejection fractions on admission, and higher mortality rates (50% vs. 15%) than B19V-negative patients. However, no cardiac outcomes differed among survivors. All six isolated B19V strains belonged to the genotype 1, representing the background virus strains isolated from five non-myocarditis controls. CONCLUSIONS: B19V-induced FM associated with epidemic strains, causing severe myocardial destruction. Rapid circulating B19V DNA testing rather than serologic testing helps guide intensive intervention for pediatric myocarditis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-025-06502-x.

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• Conserved cysteine residues in Kaposi's sarcoma herpesvirus ORF34 are necessary for viral production and viral pre-initiation complex formation.

  Watanabe T, McGraw A, Narayan K, Tibebe H, Kuriyama K, Nishimura M, Izumi T, Fujimuro M, Ohno S

  Journal of virology   98 ( 8 ) e0100024   2024.07 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

  　View Summary

  UNLABELLED: Kaposi's sarcoma herpesvirus (KSHV) ORF34 plays a significant role as a component of the viral pre-initiation complex (vPIC), which is indispensable for late gene expression across beta- and gammaherpesviruses. Although the key role of ORF34 within the vPIC and its function as a hub protein have been recognized, further clarification regarding its specific contribution to vPIC functionality and interactions with other components is required. This study employed a deep learning algorithm-assisted structural model of ORF34, revealing highly conserved amino acid residues across human beta- and gammaherpesviruses localized in structured domains. Thus, we engineered ORF34 alanine-scanning mutants by substituting conserved residues with alanine. These mutants were evaluated for their ability to interact with other vPIC factors and restore viral production in cells harboring the ORF34-deficient KSHV-BAC. Our experimental results highlight the crucial role of the four cysteine residues conserved in ORF34: a tetrahedral arrangement consisting of a pair of C-Xn-C consensus motifs. This suggests the potential incorporation of metal cations in interacting with ORF24 and ORF66 vPIC components, facilitating late gene transcription, and promoting overall virus production by capturing metal cations. In summary, our findings underline the essential role of conserved cysteines in KSHV ORF34 for effective vPIC assembly and viral replication, thereby enhancing our understanding of the complex interplay between the vPIC components. IMPORTANCE: The initiation of late gene transcription is universally conserved across the beta- and gammaherpesvirus families. This process employs a viral pre-initiation complex (vPIC), which is analogous to a cellular PIC. Although KSHV ORF34 is a critical factor for viral replication and is a component of the vPIC, the specifics of vPIC formation and the essential domains crucial for its function remain unclear. Structural predictions suggest that the four conserved cysteines (C170, C175, C256, and C259) form a tetrahedron that coordinates the metal cation. We investigated the role of these conserved amino acids in interactions with other vPIC components, late gene expression, and virus production to demonstrate for the first time that these cysteines are pivotal for such functions. This discovery not only deepens our comprehensive understanding of ORF34 and vPIC dynamics but also lays the groundwork for more detailed studies on herpesvirus replication mechanisms in future research.

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• Analysis of the interaction between the ORF42 and ORF55 proteins encoded by Kaposi's sarcoma-associated herpesvirus.

  Kuriyama K, Watanabe T, Ohno S

  Archives of virology ( Springer Science and Business Media LLC )  169 ( 5 ) 98   2024.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Lysosome-Associated Membrane Proteins Support the Furin-Mediated Processing of the Mumps Virus Fusion Protein.

  Ueo A, Kubota M, Shirogane Y, Ohno S, Hashiguchi T, Yanagi Y

  Journal of virology   94 ( 12 )   2020.06 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• A comparative epigenome analysis of gammaherpesviruses suggests cis-acting sequence features as critical mediators of rapid polycomb recruitment.

  Günther T, Fröhlich J, Herrde C, Ohno S, Burkhardt L, Adler H, Grundhoff A

  PLoS pathogens   15 ( 10 ) e1007838   2019.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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Other Papers 【 display / non-display 】

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• 麻疹ウイルスの複製に関わる新規宿主因子の同定

  伊藤美菜子, 岩崎正治, 竹田誠, 中村崇規, 柳雄介, 大野真治

  日本ウイルス学会学術集会プログラム・抄録集   60th   278   2012.10

   

  J-GLOBAL

• 麻疹ウイルス単一血溝型決定の分子基盤

  田原舞乃, BRINDLEY Melinda A, 福原秀雄, 酒井宏治, 大野真治, 駒瀬勝啓, ROTA Paul A, PLEMPER Richard K, 前仲勝実, 竹田誠

  日本ウイルス学会学術集会プログラム・抄録集   60th   282   2012.10

   

  J-GLOBAL

• 麻疹ウイルス感染認識におけるMDA5の果たす役割

  池亀聡, 竹田誠, 大野真治, 中津祐一郎, 柳雄介

  日本ウイルス学会学術集会プログラム・抄録集   57th   268   2009.10

   

  J-GLOBAL

• ポリメラーゼ遺伝子は麻疹ウイルスEdmonston株の弱毒化を担っている

  竹田誠, 大野真治, 田原舞乃, 白銀勇太, 柳雄介

  日本ウイルス学会学術集会プログラム・抄録集   56th   302   2008.10

   

  J-GLOBAL

• 麻疹ウイルスHタンパク質による受容体認識の構造基盤

  橋口隆生, 橋口隆生, 竹田誠, 田原舞乃, 池亀聡, 大野真治, 柳雄介

  日本ウイルス学会学術集会プログラム・抄録集   56th   124   2008.10

   

  J-GLOBAL

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• Grant-in-Aid for Scientific Research(C)

  Project Year: 2025.04  -  2028.03 

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2019.04  -  2022.03 

  Direct: 3,300,000 (YEN)  Overheads: 990,000 (YEN)  Total: 4,290,000 (YEN)

• Effects of mutations in HHV8 isolated form Miyakojima island, Okinawa, Japan

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2019.04  -  2022.03 

  Investigator(s): Ohno Shinji 

  Direct: 3,300,000 (YEN)  Overheads: 4,290,000 (YEN)  Total: 990,000 (YEN)

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  Human herpes virus (HHV) 8 is responsible for the development of classical Kaposi's sarcoma (KS) development. Miyakojima island (Okinawa, japan) exhibits high incidence rate of KS and is prevalent with HHV8 which has unique amino acid residue substitutions. In this study, we evaluated the influences of the substitutions in ORF72 or ORF42 upon tumorigenecity. We evaluated the cell growth of ORF72 or ORF42 expressing cells. Unfortunately, the genes did not stimulate cell proliferation of the cells we used. Further, the substitutions seen in miyakojima HHV8 did not affect the cell growth. As for ORF42, we found that this protein binds to ORF55, and HHV8 which lacks ORF42 reduces virus particle production as compared to original HHV8.

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2014.04  -  2017.03 

  Direct: 3,800,000 (YEN)  Overheads: 1,140,000 (YEN)  Total: 4,940,000 (YEN)

• Herpesvirus switching mechanism of gene regulation.

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2014.04  -  2017.03 

  Investigator(s): Ohno Shinji 

  Direct: 3,800,000 (YEN)  Overheads: 4,940,000 (YEN)  Total: 1,140,000 (YEN)

  　View Summary

  We analyzed the viral gene regulation of gammaherpesvirus. The open reading frame (ORF) 35 protein was considered to be essential for the viral growth. However, we revealed that the protein was not essential, but plays an important role for the efficiency of the viral replication. In addition, ORF35 protein was necessary for reactivation from latent infection. We also analyzed the function of ORF31 protein. And the protein was revealed to regulate viral gene expression and we identified functional domain of ORF31. Host proteins which bind to ORF31 and regulate viral replication was searched, and we found candidates. We are currently studying about these proteins.

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Joint Research activities 【 display / non-display 】

• Development of a reverse genetics system for Oitavirus

  Project Year: 2025.04  -  2026.03 

  Direct: 560,000 (YEN) 

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Social Activity 【 display / non-display 】

• 2024.08

  　

  　

• 2024.04