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Article: Ebola virus and laboratory diagnosis in Japan.

Shimojima, Masayuki

2015 Volume 65, Issue 1, Page(s) 55–60

Abstract: Ebola virus causes Ebola virus disease (EVD) with high case fatality rates in humans and has caused sporadic outbreaks with less than 500 cases. An EVD outbreak in West Africa, which probably started at the end of 2013, has an unprecedented large-scale ... ...

Abstract	Ebola virus causes Ebola virus disease (EVD) with high case fatality rates in humans and has caused sporadic outbreaks with less than 500 cases. An EVD outbreak in West Africa, which probably started at the end of 2013, has an unprecedented large-scale with more than 20,000 cases including more than 10,000 death and is still ongoing as of May 2015. National Institute of Infectious Diseases has developed laboratory diagnostic methods of EVD to detect pathogens (genes or protein) and antibodies. The methods have been recently used for suspected cases approximately once a year before the outbreak in West Africa, but after the outbreak for 7 times within this 6 months for suspected cases coming back from 3 countries of West Africa to Japan.
MeSH term(s)	Africa, Western/epidemiology ; Animals ; Civil Defense ; Clinical Laboratory Techniques/methods ; Clinical Laboratory Techniques/utilization ; Disease Outbreaks/prevention & control ; Ebolavirus/isolation & purification ; Ebolavirus/pathogenicity ; Hemorrhagic Fever, Ebola/diagnosis ; Hemorrhagic Fever, Ebola/epidemiology ; Hemorrhagic Fever, Ebola/transmission ; Hemorrhagic Fever, Ebola/virology ; Humans ; Japan ; Specimen Handling ; Travel ; Virology/methods ; Zoonoses/epidemiology ; Zoonoses/prevention & control ; Zoonoses/transmission
Language	Japanese
Publishing date	2015
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	603272-2
ISSN	0042-6857
ISSN	0042-6857
DOI	10.2222/jsv.65.55
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Article: Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries.

Kurosu, Takeshi / Sakai, Yusuke / Ami, Yasusi / Shimojima, Masayuki / Yoshikawa, Tomoki / Fukushi, Shuetsu / Nagata, Noriyo / Suzuki, Tadaki / Ebihara, Hideki / Saijo, Masayuki

Frontiers in microbiology

2024 Volume 15, Page(s) 1367672

Abstract: Introduction: Severe dengue is thought to be caused by an excessive host immune response.: Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre: Results: Although dengue virus (DENV) clinical isolates were ...

Abstract	Introduction: Severe dengue is thought to be caused by an excessive host immune response. Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre Results: Although dengue virus (DENV) clinical isolates were not virulent in LysM Cre Discussion: These observations suggest that myeloid cell infection is sufficient to trigger cytokine storm-induced vascular leakage. This model can refine the factors involved in the pathology of severe dengue leading to vascular leakage.
Language	English
Publishing date	2024-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2024.1367672
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Article ; Online: Seroprevalence for severe fever with thrombocytopenia syndrome virus among the residents of Miyazaki, Japan: An epidemiological study.

Hidaka, Kazuhiro / Mitoma, Shuya / Norimine, Junzo / Shimojima, Masayuki / Kuroda, Yoshiki / Hinoura, Takuji

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2023 Volume 30, Issue 6, Page(s) 481–487

Abstract: Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). The Miyazaki Prefecture has the highest number of SFTS cases in Japan and requires countermeasures for prevention. In ... ...

Abstract	Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). The Miyazaki Prefecture has the highest number of SFTS cases in Japan and requires countermeasures for prevention. In this study, we aimed to conduct an epidemiological survey in Miyazaki Prefecture to determine the exposure conditions of SFTSV by measuring the seroprevalence among residents of Miyazaki and to evaluate the factors that influence the endemicity of SFTS. Methods: The survey was conducted between June 2014 and April 2019 in all 26 municipalities in Miyazaki Prefecture. SFTSV antibodies were detected using an enzyme-linked immunosorbent assay in the blood samples of 6013 residents (3184 men and 2829 women). A questionnaire-based survey of the living environment was also conducted. Results: Multiple logistic regression analysis revealed that age and occupation were significant factors related to the proportion of participants with an optical density (OD) value > 0.2 and a seroprevalence of 0.9 % (54/6013). Seven seropositive individuals (0.1 %) with an OD value of >0.4 were identified (three men and four women, aged 54-69 years), and all were asymptomatic. One participant had a higher OD than the positive control. Conclusion: Although SFTS is endemic in Miyazaki Prefecture, Japan, its seroprevalence is relatively low. Since some risk areas in Miyazaki prefecture have been identified, it is important to enhance awareness of SFTS in residences and reduce contact with ticks, especially in high-risk areas.
MeSH term(s)	Male ; Humans ; Female ; Severe Fever with Thrombocytopenia Syndrome ; Japan/epidemiology ; Seroepidemiologic Studies ; Phlebovirus ; Bunyaviridae Infections
Language	English
Publishing date	2023-11-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2023.11.026
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Article ; Online: Several catechins and flavonols from green tea inhibit severe fever with thrombocytopenia syndrome virus infection in vitro.

Ogawa, Motohiko / Shimojima, Masayuki / Saijo, Masayuki / Fukasawa, Masayoshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2020 Volume 27, Issue 1, Page(s) 32–39

Abstract: Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever caused by SFTS virus (SFTSV). The mortality rate of SFTS is pretty high, but no vaccines and antiviral drugs are currently available.: Methods! ...

Abstract	Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever caused by SFTS virus (SFTSV). The mortality rate of SFTS is pretty high, but no vaccines and antiviral drugs are currently available. Methods: The antiviral effects of six green tea-related polyphenols, including four catechins and two flavonols, on SFTSV were evaluated to identify natural antiviral compounds. Results: Pretreatment with all polyphenols inhibited SFTSV infection in a concentration-dependent manner. The half-maximal inhibitory concentrations of (-)-epigallocatechin gallate (EGCg) and (-)-epigallocatechin (EGC) were 1.7-1.9 and 11-39 μM, respectively. The selectivity indices of EGCg and EGC were larger than those of the other polyphenols. Furthermore, pretreatment with EGCg and EGC dose-dependently decreased viral attachment to the host cells. Additionally, the treatment of infected cells with EGCg and EGC inhibited infection more significantly at a lower multiplicity of infection (MOI) than at a higher MOI, and this effect was less effective than that of pretreatment. Pyrogallol, a trihydroxybenzene that is the structural backbone of both EGCg and EGC, also inhibited SFTSV infection, as did gallic acid. Conclusions: Our study revealed that green tea-related polyphenols, especially EGCg and EGC, are useful as candidate anti-SFTSV drugs. Furthermore, the structural basis of their antiviral activity was identified, which should enable investigations of more active drugs in the future.
MeSH term(s)	Catechin/pharmacology ; Flavonols ; Hemorrhagic Fevers, Viral ; Humans ; Severe Fever with Thrombocytopenia Syndrome ; Tea
Chemical Substances	Flavonols ; Tea ; Catechin (8R1V1STN48)
Language	English
Publishing date	2020-08-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2020.08.005
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Article ; Online: The nonstructural p17 protein of a fusogenic bat-borne reovirus regulates viral replication in virus species- and host-specific manners.

Nouda, Ryotaro / Kawagishi, Takahiro / Kanai, Yuta / Shimojima, Masayuki / Saijo, Masayuki / Matsuura, Yoshiharu / Kobayashi, Takeshi

PLoS pathogens

2022 Volume 18, Issue 6, Page(s) e1010553

Abstract: Nelson Bay orthoreovirus (NBV), a member of the family Reoviridae, genus Orthoreovirus, is a bat-borne virus that causes respiratory diseases in humans. NBV encodes two unique nonstructural proteins, fusion-associated small transmembrane (FAST) protein ... ...

Abstract	Nelson Bay orthoreovirus (NBV), a member of the family Reoviridae, genus Orthoreovirus, is a bat-borne virus that causes respiratory diseases in humans. NBV encodes two unique nonstructural proteins, fusion-associated small transmembrane (FAST) protein and p17 protein, in the S1 gene segment. FAST induces cell-cell fusion between infected cells and neighboring cells and the fusogenic activity is required for efficient viral replication. However, the function of p17 in the virus cycle is not fully understood. Here, various p17 mutant viruses including p17-deficient viruses were generated by a reverse genetics system for NBV. The results demonstrated that p17 is not essential for viral replication and does not play an important role in viral pathogenesis. On the other hand, NBV p17 regulated viral replication in a bat cell line but not in other human and animal cell lines. Nuclear localization of p17 is associated with the regulation of NBV replication in bat cells. We also found that p17 dramatically enhances the cell-cell fusion activity of NBV FAST protein for efficient replication in bat cells. Furthermore, we found that a protein homologue of NBV p17 from another bat-borne orthoreovirus, but not those of avian orthoreovirus or baboon orthoreovirus, also supported efficient viral replication in bat cells using a p17-deficient virus-based complementation approach. These results provide critical insights into the functioning of the unique replication machinery of bat-borne viruses in their natural hosts.
MeSH term(s)	Animals ; Antibodies, Viral ; Chiroptera ; DNA Viruses ; Orthoreovirus/genetics ; Reoviridae ; Virus Replication
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2022-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010553
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Article ; Online: Protocol of Tecopox study: a multicentre, open-label, double-arm trial to evaluate the efficacy and safety of oral tecovirimat therapy for patients with smallpox or monkeypox.

Suzuki, Tetsuya / Saito, Sho / Tsuzuki, Shinya / Ashida, Shinobu / Takakusaki, Mizue / Yoshikawa, Tomoki / Shimojima, Masayuki / Ebihara, Hideki / Ohmagari, Norio / Morioka, Shinichiro

BMJ open

2023 Volume 13, Issue 8, Page(s) e069550

Abstract: Introduction: Monkeypox was originally endemic locally in West Africa; however, outbreaks in non-endemic countries have been recognised since May 2022. The effectiveness of tecovirimat has been estimated against smallpox, which belongs to the same : ... ...

Abstract	Introduction: Monkeypox was originally endemic locally in West Africa; however, outbreaks in non-endemic countries have been recognised since May 2022. The effectiveness of tecovirimat has been estimated against smallpox, which belongs to the same Methods and analysis: This nationwide, multicentre, non-randomised, open-label, double-arm study will involve viral examination of the blood, throat swabs, urine and skin lesions, performed periodically. Participants will freely decide whether to participate in an administered group (supportive treatment plus oral tecovirimat) or a non-administered group (only supportive treatment). Tecovirimat will be administered for 14 days. To ensure that financial problems do not preclude participation in the study, the research fund will cover the cost of tecovirimat and basic hospitalisation fees. The primary endpoint is the percentage of patients with negative PCR results (cycle threshold value ≥40) for skin lesion specimens at 14 days after inclusion in the study. Secondary endpoints include mortality at 14 and 30 days, viral load in each sample, duration of fever and adverse events. The sample size is estimated to be 50 patients with monkeypox or smallpox. Ethics and dissemination: Written informed consent will be obtained from all participants. This study was approved by the Certified Review Board of National Center for Global Health and Medicine and published in the Japan Registry of Clinical Trials. The results of this study will be published in peer-reviewed journals and/or in presentations at academic conferences. Trial registration number: jRCTs031220169.
MeSH term(s)	Humans ; COVID-19 ; Mpox (monkeypox)/drug therapy ; Smallpox/drug therapy ; SARS-CoV-2 ; Antiviral Agents/adverse effects ; Benzamides/adverse effects ; Multicenter Studies as Topic
Chemical Substances	Antiviral Agents ; Benzamides
Language	English
Publishing date	2023-08-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-069550
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Article: Rapid whole genome sequencing methods for RNA viruses.

Misu, Masayasu / Yoshikawa, Tomoki / Sugimoto, Satoko / Takamatsu, Yuki / Kurosu, Takeshi / Ouji, Yukiteru / Yoshikawa, Masahide / Shimojima, Masayuki / Ebihara, Hideki / Saijo, Masayuki

Frontiers in microbiology

2023 Volume 14, Page(s) 1137086

Abstract: RNA viruses are the etiological agents of many infectious diseases. Since RNA viruses are error-prone during genome replication, rapid, accurate and economical whole RNA viral genome sequence determination is highly demanded. Next-generation sequencing ( ... ...

Abstract	RNA viruses are the etiological agents of many infectious diseases. Since RNA viruses are error-prone during genome replication, rapid, accurate and economical whole RNA viral genome sequence determination is highly demanded. Next-generation sequencing (NGS) techniques perform whole viral genome sequencing due to their high-throughput sequencing capacity. However, the NGS techniques involve a significant burden for sample preparation. Since to generate complete viral genome coverage, genomic nucleic acid enrichment is required by reverse transcription PCR using virus-specific primers or by viral particle concentration. Furthermore, conventional NGS techniques cannot determine the 5' and 3' terminal sequences of the RNA viral genome. Therefore, the terminal sequences are determined one by one using rapid amplification of cDNA ends (RACE). However, since some RNA viruses have segmented genomes, the burden of the determination using RACE is proportional to the number of segments. To date, there is only one study attempting whole genome sequencing of multiple RNA viruses without using above mentioned methods, but the generated sequences' accuracy compared to the reference sequences was up to 97% and did not reach 100% due to the low read depth. Hence, we established novel methods, named PCR-NGS and RCA-NGS, that were optimized for an NGS machine, MinION. These methods do not require nucleic acid amplification with virus-specific PCR primers, physical viral particle enrichment, and RACE. These methods enable whole RNA viral genome sequencing by combining the following techniques: (1) removal of unwanted DNA and RNA other than the RNA viral genome by nuclease treatment; (2) the terminal of viral genome sequence determination by barcoded linkers ligation; (3) amplification of the viral genomic cDNA using ligated linker sequences-specific PCR or an isothermal DNA amplification technique, such as rolling circle amplification (RCA). The established method was evaluated using isolated RNA viruses with single-stranded, double-stranded, positive-stranded, negative-stranded, non-segmented or multi-segmented genomes. As a result, all the viral genome sequences could be determined with 100% accuracy, and these mean read depths were greater than 2,500×, at least using either of the methods. This method should allow for easy and economical determination of accurate RNA viral genomes.
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1137086
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Article: Markerless bacterial artificial chromosome manipulation method by red proteins of phage λ mediated homologous recombination utilizing fluorescent proteins for both positive and counter selection.

Yoshikawa, Tomoki / Misu, Masayasu / Kurosu, Takeshi / Takamatsu, Yuki / Sugimoto, Satoko / Shimojima, Masayuki / Ebihara, Hideki / Saijo, Masayuki

Heliyon

2023 Volume 9, Issue 8, Page(s) e18983

Abstract: Manipulating viral genomes is an essential technique in reverse genetics and recombinant vaccine development. A strategy for manipulating large viral genomes involves introducing their entire genome into bacterial artificial chromosomes and ... ...

Abstract	Manipulating viral genomes is an essential technique in reverse genetics and recombinant vaccine development. A strategy for manipulating large viral genomes involves introducing their entire genome into bacterial artificial chromosomes and employing
Language	English
Publishing date	2023-08-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e18983
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Article ; Online: The combination of levodopa with levodopa-metabolizing enzyme inhibitors prevents severe fever with thrombocytopenia syndrome virus infection in vitro more effectively than single levodopa.

Ogawa, Motohiko / Murae, Mana / Mizukami, Tomoharu / Gemba, Ryutaro / Irie, Takuya / Shimojima, Masayuki / Ebihara, Hideki / Noguchi, Kohji / Fukasawa, Masayoshi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

2023 Volume 29, Issue 5, Page(s) 549–553

Abstract: Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus, is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al. (2022) reported that ... ...

Abstract	Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus, is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al. (2022) reported that levodopa, an antiparkinsonian drug with an o-dihydroxybenzene backbone, which is important for anti-SFTSV activity, inhibited SFTSV infection. Levodopa is metabolized by dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) in vivo. We evaluated the anti-SFTSV efficacy of two DDC inhibitors, benserazide hydrochloride and carbidopa, and two COMT inhibitors, entacapone and nitecapone, which also have an o-dihydroxybenzene backbone. Only DDC inhibitors inhibited SFTSV infection with pretreatment of the virus (half-maximal inhibitory concentration [IC
MeSH term(s)	Humans ; Levodopa/pharmacology ; Levodopa/therapeutic use ; Carbidopa ; Catechol O-Methyltransferase/metabolism ; Severe Fever with Thrombocytopenia Syndrome/drug therapy ; Catechols/pharmacology ; Catechols/therapeutic use ; Enzyme Inhibitors/therapeutic use ; Phlebovirus
Chemical Substances	Levodopa (46627O600J) ; entacapone (4975G9NM6T) ; Carbidopa (MNX7R8C5VO) ; Catechol O-Methyltransferase (EC 2.1.1.6) ; Catechols ; Enzyme Inhibitors
Language	English
Publishing date	2023-03-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1355399-9
ISSN	1437-7780 ; 1341-321X
ISSN (online)	1437-7780
ISSN	1341-321X
DOI	10.1016/j.jiac.2023.02.017
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Article ; Online: The Nonstructural Protein NSs of Severe Fever with Thrombocytopenia Syndrome Virus Causes a Cytokine Storm through the Hyperactivation of NF-κB

Khalil, Jumana / Yamada, Shintarō / Tsukamoto, Yuta / Abe, Hiroto / Shimojima, Masayuki / Kato, Hiroki / Fujita, Takashi

Molecular and Cellular Biology. 2021 Mar. 1, v. 41, no. 3 p.e00542-20-

2021

Abstract: Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging highly pathogenic phlebovirus. The syndrome is characterized by the substantial production of inflammatory cytokines and chemokines, described as a cytokine storm, which ... ...

Abstract	Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging highly pathogenic phlebovirus. The syndrome is characterized by the substantial production of inflammatory cytokines and chemokines, described as a cytokine storm, which correlates with multiorgan failure and high mortality. SFSTV nonstructural (NSs) protein was suggested to mediate the pathogenesis by inhibiting antiviral interferon signaling in the host. However, whether SFTSV NSs protein mediates the induction of a fatal cytokine storm remains unaddressed. We demonstrated that SFTSV NSs promotes the hyperinduction of cytokine/chemokine genes in vitro, reminiscent of a cytokine storm. Using gene deletion and pharmacological intervention, we found that the induced cytokine storm is driven by the transcription factor NF-κB. Our investigation revealed that TANK-binding kinase 1 (TBK1) suppresses NF-κB signaling and cytokine/chemokine induction in a kinase activity-dependent manner and that NSs sequesters TBK1 to prevent it from suppressing NF-κB, thereby promoting the activation of NF-κB and its target cytokine/chemokine genes. Of note, NF-κB inhibition suppressed the induction of proinflammatory cytokines in SFTSV-infected type I interferon (IFN-I) receptor 1-deficient (Ifnar1⁻/⁻) mice. These findings establish the essential role of NSs in SFTS pathogenesis and suggest NF-κB as a possible therapeutic target.
Keywords	Huaiyangshan banyangvirus ; Phlebovirus ; cell biology ; chemokines ; gene deletion ; interferons ; mortality ; pathogenesis ; severe fever with thrombocytopenia syndrome ; therapeutics ; transcription factors ; viral nonstructural proteins ; viruses ; SFTSV NSs ; NF-κB ; cytokine storm ; TBK1 ; viral pathogenesis
Language	English
Dates of publication	2021-0301
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00542-20
Database	NAL-Catalogue (AGRICOLA)

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