2023/09/25 更新

写真a

イワナミ ショウヤ
岩波 翔也
IWANAMI Shoya
所属
大学院理学研究科 理学専攻 生命理学 講師
大学院担当
大学院理学研究科
学部担当
理学部 生命理学科
職名
講師
連絡先
メールアドレス
外部リンク

学位 1

  1. 博士(理学) ( 2020年9月   九州大学 ) 

研究キーワード 3

  1. ウイルス感染動態

  2. 数理モデル

  3. 造血幹細胞

研究分野 3

  1. 自然科学一般 / 生物物理、化学物理、ソフトマターの物理  / 数理生物

  2. 自然科学一般 / 応用数学、統計数学

  3. ライフサイエンス / 生物物理学  / 数理生物学

現在の研究課題とSDGs 1

  1. 数理科学による感染症の理解

経歴 6

  1. 名古屋大学   大学院理学研究科 理学専攻   講師

    2023年4月 - 現在

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    国名:日本国

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  2. 名古屋大学   大学院理学研究科 理学専攻   助教

    2022年4月 - 2023年3月

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    国名:日本国

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  3. 名古屋大学   大学院理学研究科生命理学専攻   助教

    2021年4月 - 2022年3月

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    国名:日本国

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  4. 九州大学   大学院理学研究院生物科学部門   学術研究員   特任助教

    2020年12月 - 2021年3月

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    国名:日本国

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  5. 九州大学   大学院理学研究院生物科学部門   学術研究員

    2020年10月 - 2020年11月

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    国名:日本国

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  6. 九州大学   大学院システム生命科学府   日本学術振興会特別研究員DC2

    2019年4月 - 2020年9月

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    国名:日本国

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▼全件表示

学歴 1

  1. 九州大学   大学院システム生命科学府   システム生命科学専攻

    2016年4月 - 2020年9月

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    国名: 日本国

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所属学協会 5

  1. 日本免疫学会

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  2. 日本分子生物学会

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  3. 日本数理生物学会

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  4. 日本骨免疫学会

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  5. 日本ウイルス学会

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論文 25

  1. Potential Anti-Mpox Virus Activity of Atovaquone, Mefloquine, and Molnupiravir, and Their Potential Use as Treatments 査読有り 国際共著 国際誌

    Akazawa D., Ohashi H., Hishiki T., Morita T., Iwanami S., Kim K.S., Jeong Y.D., Park E.S., Kataoka M., Shionoya K., Mifune J., Tsuchimoto K., Ojima S., Azam A.H., Nakajima S., Park H., Yoshikawa T., Shimojima M., Kiga K., Iwami S., Maeda K., Suzuki T., Ebihara H., Takahashi Y., Watashi K.

    The Journal of infectious diseases   228 巻 ( 5 ) 頁: 591 - 603   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The Journal of infectious diseases  

    BACKGROUND: Mpox virus (MPXV) is a zoonotic orthopoxvirus and caused an outbreak in 2022. Although tecovirimat and brincidofovir are approved as anti-smallpox drugs, their effects in mpox patients have not been well documented. In this study, by a drug repurposing approach, we identified potential drug candidates for treating mpox and predicted their clinical impacts by mathematical modeling. METHODS: We screened 132 approved drugs using an MPXV infection cell system. We quantified antiviral activities of potential drug candidates by measuring intracellular viral DNA and analyzed the modes of action by time-of-addition assay and electron microscopic analysis. We further predicted the efficacy of drugs under clinical concentrations by mathematical simulation and examined combination treatment. RESULTS: Atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of 0.51-5.2 μM, which was more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and molnupiravir targeted postentry processes. Atovaquone was suggested to exert its activity through inhibiting dihydroorotate dehydrogenase. Combining atovaquone with tecovirimat enhanced the anti-MPXV effect of tecovirimat. Quantitative mathematical simulations predicted that atovaquone can promote viral clearance in patients by 7 days at clinically relevant drug concentrations. CONCLUSIONS: These data suggest that atovaquone would be a potential candidate for treating mpox.

    DOI: 10.1093/infdis/jiad058

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  2. A Multicenter Randomized Controlled Trial To Evaluate the Efficacy and Safety of Nelfinavir in Patients with Mild COVID-19 査読有り

    Miyazaki T., Hosogaya N., Fukushige Y., Takemori S., Morimoto S., Yamamoto H., Hori M., Ozawa Y., Shiko Y., Inaba Y., Kurokawa T., Hanaoka H., Iwanami S., Kim K., Iwami S., Watashi K., Miyazawa K., Umeyama T., Yamagoe S., Miyazaki Y., Wakita T., Sumiyoshi M., Hirayama T., Izumikawa K., Yanagihara K., Mukae H., Kawasuji H., Yamamoto Y., Tarumoto N., Ishii H., Ohno H., Yatera K., Kakeya H., Kichikawa Y., Kato Y., Matsumoto T., Saito M., Yotsuyanagi H., Kohno S.

    Microbiology Spectrum   11 巻 ( 3 ) 頁: e0431122   2023年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Microbiology Spectrum  

    Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were randomly assigned (1:1) to receive oral nelfinavir (750 mg; thrice daily for 14 days) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to viral clearance, confirmed using quantitative reverse-transcription PCR by assessors blinded to the assigned treatment. A total of 123 patients (63 in the nelfinavir group and 60 in the control group) were included. The median time to viral clearance was 8.0 (95% confidence interval [CI], 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI, 7.0 to 10.0) days in the control group, with no significant difference between the treatment groups (hazard ratio, 0.815; 95% CI, 0.563 to 1.182; P = 0.1870). Adverse events were reported in 47 (74.6%) and 20 (33.3%) patients in the nelfinavir and control groups, respectively. The most common adverse event in the nelfinavir group was diarrhea (49.2%). Nelfinavir did not reduce the time to viral clearance in this setting. Our findings indicate that nelfinavir should not be recommended in asymptomatic or mildly symptomatic patients infected with SARS-CoV-2. The study is registered with the Japan Registry of Clinical Trials (jRCT2071200023). IMPORTANCE The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. However, its efficacy in patients with COVID-19 has not been studied. We conducted a multicenter, randomized controlled trial to evaluate the efficacy and safety of orally administered nelfinavir in patients with asymptomatic or mildly symptomatic COVID-19. Compared to standard-of-care alone, nelfinavir (750 mg, thrice daily) did not reduce the time to viral clearance, viral load, or the time to resolution of symptoms. More patients had adverse events in the nelfinavir group than in the control group (74.6% [47/63 patients] versus 33.3% [20/60 patients]). Our clinical study provides evidence that nelfinavir, despite its antiviral effects on SARSCoV-2 in vitro, should not be recommended for the treatment of patients with COVID-19 having no or mild symptoms.

    DOI: 10.1128/spectrum.04311-22

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  3. Relationship between the inclusion/exclusion criteria and sample size in randomized controlled trials for SARS-CoV-2 entry inhibitors 査読有り 国際誌

    Tatematsu D., Akao M., Park H., Iwami S., Ejima K., Iwanami S.

    Journal of Theoretical Biology   561 巻   頁: 111403 - 111403   2023年3月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Theoretical Biology  

    The coronavirus disease 2019 (COVID-19) pandemic that has been ongoing since 2019 is still ongoing and how to control it is one of the international issues to be addressed. Antiviral drugs that reduce the viral load in terms of reducing the risk of secondary infection are important. For the general control of emerging infectious diseases, establishing an efficient method to evaluate candidate therapeutic agents will lead to a rapid response. We evaluated clinical trial designs for viral entry inhibitors that have the potential to be effective pre-exposure prophylactic drugs in addition to reducing viral load after infection. We used a previously developed simulation of clinical trials based on a mathematical model of within-host viral infection dynamics to evaluate sample sizes in clinical trials of viral entry inhibitors against COVID-19. We assumed four measures as outcomes, namely change in log10-transformed viral load from symptom onset, PCR positive ratio, log10-transformed viral load, and cumulative viral load, and then sample sizes were calculated for drugs with 99 % and 95 % antiviral efficacy. Consistent with previous results, we found that sample sizes could be dramatically reduced for all outcomes used in an analysis by adopting inclusion/exclusion criteria such that only patients in the early post-infection period would be included in a clinical trial. A comparison of sample sizes across outcomes demonstrated an optimal measurement schedule associated with the nature of the outcome measured for the evaluation of drug efficacy. In particular, the sample sizes calculated from the change in viral load and from viral load tended to be small when measurements were taken at earlier time points after treatment initiation. For the cumulative viral load, the sample size was lower than that from the other outcomes when the stricter inclusion/exclusion criteria to include patients whose time since onset is earlier than 2 days was used. We concluded that the design of efficient clinical trials should consider the inclusion/exclusion criteria and measurement schedules, as well as outcome selection based on sample size, personnel and budget needed to conduct the trial, and the importance of the outcome regarding the medical and societal requirements. This study provides insights into clinical trial design for a variety of situations, especially addressing infectious disease prevalence and feasible trial sizes. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”.

    DOI: 10.1016/j.jtbi.2022.111403

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  4. Increased flexibility of the SARS-CoV-2 RNA-binding site causes resistance to remdesivir 査読有り

    Torii S., Kim K.S., Koseki J., Suzuki R., Iwanami S., Fujita Y., Jeong Y.D., Ito J., Asakura H., Nagashima M., Sadamasu K., Yoshimura K., Sato K., Matsuura Y., Shimamura T., Iwami S., Fukuhara T.

    PLoS Pathogens   19 巻 ( 3 ) 頁: e1011231 - e1011231   2023年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PLoS Pathogens  

    Mutations continue to accumulate within the SARS-CoV-2 genome, and the ongoing epidemic has shown no signs of ending. It is critical to predict problematic mutations that may arise in clinical environments and assess their properties in advance to quickly implement countermeasures against future variant infections. In this study, we identified mutations resistant to remdesivir, which is widely administered to SARS-CoV-2-infected patients, and discuss the cause of resistance. First, we simultaneously constructed eight recombinant viruses carrying the mutations detected in in vitro serial passages of SARS-CoV-2 in the presence of remdesivir. We confirmed that all the mutant viruses didn’t gain the virus production efficiency without remdesivir treatment. Time course analyses of cellular virus infections showed significantly higher infectious titers and infection rates in mutant viruses than wild type virus under treatment with remdesivir. Next, we developed a mathematical model in consideration of the changing dynamic of cells infected with mutant viruses with distinct propagation properties and defined that mutations detected in in vitro passages canceled the antiviral activities of remdesivir without raising virus production capacity. Finally, molecular dynamics simulations of the NSP12 protein of SARS-CoV-2 revealed that the molecular vibration around the RNA-binding site was increased by the introduction of mutations on NSP12. Taken together, we identified multiple mutations that affected the flexibility of the RNA binding site and decreased the antiviral activity of remdesivir. Our new insights will contribute to developing further antiviral measures against SARS-CoV-2 infection.

    DOI: 10.1371/journal.ppat.1011231

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  5. Designing isolation guidelines for COVID-19 patients with rapid antigen tests 査読有り 国際共著 国際誌

    Jeong Y.D., Ejima K., Kim K.S., Joohyeon W., Iwanami S., Fujita Y., Jung I.H., Aihara K., Shibuya K., Iwami S., Bento A.I., Ajelli M.

    Nature Communications   13 巻 ( 1 ) 頁: 4910 - 4910   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Communications  

    Appropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adopted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation, whereas others may still be infectious. Utilizing viral test results to determine isolation length would minimize both the risk of prematurely ending isolation of infectious patients and the unnecessary individual burden of redundant isolation of noninfectious patients. In this study, we develop a data-driven computational framework to compute the population-level risk and the burden of different isolation guidelines with rapid antigen tests (i.e., lateral flow tests). Here, we show that when the detection limit is higher than the infectiousness threshold values, additional consecutive negative results are needed to ascertain infectiousness status. Further, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation.

    DOI: 10.1038/s41467-022-32663-9

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  6. Estimation of timing of infection from longitudinal SARS-CoV-2 viral load data: mathematical modelling study 査読有り 国際共著 国際誌

    Ejima K., Kim K.S., Bento A.I., Iwanami S., Fujita Y., Aihara K., Shibuya K., Iwami S.

    BMC Infectious Diseases   22 巻 ( 1 ) 頁: 656 - 656   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Infectious Diseases  

    Background: Multiple waves of the COVID-19 epidemic have hit most countries by the end of 2021. Most of those waves are caused by emergence and importation of new variants. To prevent importation of new variants, combination of border control and contact tracing is essential. However, the timing of infection inferred by interview is influenced by recall bias and hinders the contact tracing process. Methods: We propose a novel approach to infer the timing of infection, by employing a within-host model to capture viral load dynamics after the onset of symptoms. We applied this approach to ascertain secondary transmission which can trigger outbreaks. As a demonstration, the 12 initial reported cases in Singapore, which were considered as imported because of their recent travel history to Wuhan, were analyzed to assess whether they are truly imported. Results: Our approach suggested that 6 cases were infected prior to the arrival in Singapore, whereas other 6 cases might have been secondary local infection. Three among the 6 potential secondary transmission cases revealed that they had contact history to previously confirmed cases. Conclusions: Contact trace combined with our approach using viral load data could be the key to mitigate the risk of importation of new variants by identifying cases as early as possible and inferring the timing of infection with high accuracy.

    DOI: 10.1186/s12879-022-07646-2

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  7. Mathematical Modeling and Analysis of Aging Alteration of Hematopoietic Stem Cell Symmetric and Asymmetric Division

    Kawahigashi Teiko, Iwanami Shoya, Iwami Shingo, Yamazaki Satoshi

    BLOOD   140 巻   頁: 8613 - 8613   2022年11月

  8. Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2 査読有り 国際共著 国際誌

    Ohashi H., Hishiki T., Akazawa D., Kim K.S., Woo J., Shionoya K., Tsuchimoto K., Iwanami S., Moriyama S., Kinoshita H., Yamada S., Kuroda Y., Yamamoto T., Kishida N., Watanabe S., Hasegawa H., Ebihara H., Suzuki T., Maeda K., Fukushi S., Takahashi Y., Iwami S., Watashi K.

    Antiviral Research   205 巻   頁: 105372 - 105372   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Antiviral Research  

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 has spread in many countries, replacing the earlier Omicron subvariant BA.1 and other variants. Here, using a cell culture infection assay, we quantified the intrinsic sensitivity of BA.2 and BA.1 compared with other variants of concern, Alpha, Gamma, and Delta, to five approved-neutralizing antibodies and antiviral drugs. Our assay revealed the diverse sensitivities of these variants to antibodies, including the loss of response of both BA.1 and BA.2 to casirivimab and of BA.1 to imdevimab. In contrast, EIDD-1931 and nirmatrelvir showed a more conserved activities to these variants. The viral response profile combined with mathematical analysis estimated differences in antiviral effects among variants in the clinical concentrations. These analyses provide essential evidence that gives insight into variant emergence's impact on choosing optimal drug treatment.

    DOI: 10.1016/j.antiviral.2022.105372

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  9. Factors Associated with COVID-19 Vaccine Booster Hesitancy: A Retrospective Cohort Study, Fukushima Vaccination Community Survey 査読有り 国際誌

    Yoshida M., Kobashi Y., Kawamura T., Shimazu Y., Nishikawa Y., Omata F., Zhao T., Yamamoto C., Kaneko Y., Nakayama A., Takita M., Ito N., Kawashima M., Sugiura S., Shibuya K., Iwami S., Kim K., Iwanami S., Kodama T., Tsubokura M.

    Vaccines   10 巻 ( 4 ) 頁: 515 - 515   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Vaccines  

    This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive a third dose of a coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. This study included participants who provided answers in the questionnaire about whether they had an intent to receive a third dose of a vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate over the booster vaccination were retrieved. Among the 2439 participants, with a mean (±SD) age of 52.6 ± 18.9 years, and a median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that participants of a younger age (OR = 0.98; 95% CI: 0.96–1.00) and with a higher antibody level (OR = 2.52; 95% CI: 1.27–4.99) were positively associated with hesitancy over the third vaccine. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had a significant impact on behavior regarding the third vaccination. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken with these groups that are likely to hesitate over the third vaccine, subsequently increasing booster contact rate.

    DOI: 10.3390/vaccines10040515

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  10. Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection 査読有り 国際共著 国際誌

    Kumata R., Iwanami S., Mar K.B., Kakizoe Y., Misawa N., Nakaoka S., Koyanagi Y., Perelson A.S., Schoggins J.W., Iwami S., Sato K.

    PLoS Computational Biology   18 巻 ( 4 ) 頁: e1010053   2022年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PLoS Computational Biology  

    In HIV-1-infected individuals, transmitted/founder (TF) virus contributes to establish new infection and expands during the acute phase of infection, while chronic control (CC) virus emerges during the chronic phase of infection. TF viruses are more resistant to interferon-alpha (IFN-α)-mediated antiviral effects than CC virus, however, its virological relevance in infected individuals remains unclear. Here we perform an experimental-mathematical investigation and reveal that IFN-α strongly inhibits cell-to-cell infection by CC virus but only weakly affects that by TF virus. Surprisingly, IFN-α enhances cell-free infection of HIV-1, particularly that of CC virus, in a virus-cell density-dependent manner. We further demonstrate that LY6E, an IFN-stimulated gene, can contribute to the density-dependent enhancement of cell-free HIV-1 infection. Altogether, our findings suggest that the major difference between TF and CC viruses can be explained by their resistance to IFN-α-mediated inhibition of cell-to-cell infection and their sensitivity to IFN-α-mediated enhancement of cell-free infection.

    DOI: 10.1371/journal.pcbi.1010053

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  11. Characterization of various remdesivir-resistant mutations of SARS-CoV-2 by mathematical modeling and molecular dynamics simulation

    Shiho Torii, Kwang Su Kim, Jun Koseki, Rigel Suzuki, Shoya Iwanami, Yasuhisa Fujita, Yong Dam Jeong, Yoshiharu Matsuura, Teppei Shimamura, Shingo Iwami, Takasuke Fukuhara

        2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cold Spring Harbor Laboratory  

    DOI: 10.1101/2022.02.22.481436

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  12. Designing isolation guidelines for COVID-19 patients utilizing rapid antigen tests: a simulation study using viral dynamics models.

    Jeong YD, Ejima K, Kim KS, Joohyeon W, Iwanami S, Fujita Y, Jung IH, Shibuya K, Iwami S, Bento AI, Ajelli M

    medRxiv : the preprint server for health sciences     2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1101/2022.01.24.22269769

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  13. Detection of significant antiviral drug effects on COVID-19 using viral load and PCR-positive rate in randomized controlled trials 査読有り

    Marwa AKAO, Joohyeon WOO, Shingo IWAMI, Shoya IWANAMI

    Translational and Regulatory Sciences   3 巻 ( 3 ) 頁: 85 - 88   2021年12月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMED iD3 Catalyst Unit  

    <p>To evaluate the effects of antiviral drugs against coronavirus disease (COVID-19), we calculated the sample size needed to detect significant differences in daily viral load in randomized controlled trials. While calculating sample sizes, simulated viral loads that mimicked longitudinal clinical data were used. The sample size computed from the viral load was the smallest 2 to 4 days after trial participation, while the smallest sample size computed from the positive rate was 4 to 7 days after clinical trial participation.</p>

    DOI: 10.33611/trs.2021-025

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  14. UNDERSTANDING OF HEMATOPOIETIC STEM CELL SYMMETRIC AND ASYMMETRIC DIVISION TRANSITION BY AGING USING MATHEMATICAL MODELING

    Kawahigashi Teiko, Iwami Shingo, Yamazaki Satoshi, Iwanami Shoya

    EXPERIMENTAL HEMATOLOGY   100 巻   頁: S80 - S80   2021年8月

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  15. Incomplete antiviral treatment may induce longer durations of viral shedding during SARS-CoV-2 infection 査読有り

    Kim K.S., Iwanami S., Oda T., Fujita Y., Kuba K., Miyazaki T., Ejima K., Iwami S.

    Life Science Alliance   4 巻 ( 10 ) 頁: e202101049 - e202101049   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Life Science Alliance  

    The duration of viral shedding is determined by a balance between de novo infection and removal of infected cells. That is, if infection is completely blocked with antiviral drugs (100% inhibition), the duration of viral shedding is minimal and is determined by the length of virus production. However, some mathematical models predict that if infected individuals are treated with antiviral drugs with efficacy below 100%, viral shedding may last longer than without treatment because further de novo infections are driven by entry of the virus into partially protected, uninfected cells at a slower rate. Using a simple mathematical model, we quantified SARS-CoV-2 infection dynamics in non-human primates and characterized the kinetics of viral shedding. We counterintuitively found that treatments initiated early, such as 0.5 d after virus inoculation, with intermediate to relatively high efficacy (30-70% inhibition of virus replication) yield a prolonged duration of viral shedding (by about 6.0 d) compared with no treatment.

    DOI: 10.26508/LSA.202101049

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  16. Revisiting the guidelines for ending isolation for covid-19 patients 査読有り 国際共著

    Jeong Y.D., Ejima K., Kim K.S., Iwanami S., Bento A.I., Fujita Y., Jung I.H., Aihara K., Watashi K., Miyazaki T., Wakita T., Iwami S., Ajelli M.

    eLife   10 巻   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:eLife  

    Since the start of the COVID-19 pandemic, two mainstream guidelines for defining when to end the isolation of SARS-CoV-2-infected individuals have been in use: the one-size-fits-all approach (i.e. patients are isolated for a fixed number of days) and the personalized approach (i.e. based on repeated testing of isolated patients). We use a mathematical framework to model within-host viral dynamics and test different criteria for ending isolation. By considering a fixed time of 10 days since symptom onset as the criterion for ending isolation, we estimated that the risk of releasing an individual who is still infectious is low (0–6.6%). However, this policy entails lengthy unnecessary isolations (4.8–8.3 days). In contrast, by using a personalized strategy, similar low risks can be reached with shorter prolonged isolations. The obtained findings provide a scientific rationale for policies on ending the isolation of SARS-CoV-2-infected individuals.

    DOI: 10.7554/eLife.69340

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  17. Detection of significant antiviral drug effects on COVID-19 with reasonable sample sizes in randomized controlled trials: A modeling study 査読有り

    Iwanami S., Ejima K., Su Kim K., Noshita K., Fujita Y., Miyazaki T., Kohno S., Miyazaki Y., Morimoto S., Nakaoka S., Koizumi Y., Asai Y., Aihara K., Watashi K., Thompson R.N., Shibuya K., Fujiu K., Perelson A.S., Iwami S., Wakita T.

    PLoS Medicine   18 巻 ( 7 ) 頁: e1003660 - e1003660   2021年7月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PLoS Medicine  

    Background Development of an effective antiviral drug for Coronavirus Disease 2019 (COVID-19) is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence from clinical studies is limited. The lack of evidence from clinical trials may stem in part from the imperfect design of the trials. We investigated how clinical trials for antivirals need to be designed, especially focusing on the sample size in randomized controlled trials Methods and findings A modeling study was conducted to help understand the reasons behind inconsistent clinical trial findings and to design better clinical trials. We first analyzed longitudinal viral load data for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) without antiviral treatment by use of a within-host virus dynamics model. The fitted viral load was categorized into 3 different groups by a clustering approach. Comparison of the estimated parameters showed that the 3 distinct groups were characterized by different virus decay rates (p-value < 0.001). The mean decay rates were 1.17 d-1 (95% CI: 1.06 to 1.27 d-1), 0.777 d-1 (0.716 to 0.838 d-1), and 0.450 d-1 (0.378 to 0.522 d-1) for the 3 groups, respectively. Such heterogeneity in virus dynamics could be a confounding variable if it is associated with treatment allocation in compassionate use programs (i.e., observational studies). Subsequently, we mimicked randomized controlled trials of antivirals by simulation. An antiviral effect causing a 95% to 99% reduction in viral replication was added to the model. To be realistic, we assumed that randomization and treatment are initiated with some time lag after symptom onset. Using the duration of virus shedding as an outcome, the sample size to detect a statistically significant mean difference between the treatment and placebo groups (1:1 allocation) was 13,603 and 11,670 (when the antiviral effect was 95% and 99%, respectively) per group if all patients are enrolled regardless of timing of randomization. The sample size was reduced to 584 and 458 (when the antiviral effect was 95% and 99%, respectively) if only patients who are treated within 1 day of symptom onset are enrolled. We confirmed the sample size was similarly reduced when using cumulative viral load in log scale as an outcome. We used a conventional virus dynamics model, which may not fully reflect the detailed mechanisms of viral dynamics of SARS-CoV-2. The model needs to be calibrated in terms of both parameter settings and model structure, which would yield more reliable sample size calculation. Conclusions In this study, we found that estimated association in observational studies can be biased due to large heterogeneity in viral dynamics among infected individuals, and statistically significant effect in randomized controlled trials may be difficult to be detected due to small sample size. The sample size can be dramatically reduced by recruiting patients immediately after developing symptoms. We believe this is the first study investigated the study design of clinical trials for antiviral treatment using the viral dynamics model.

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  18. Estimation of the incubation period of COVID-19 using viral load data 査読有り 国際誌

    Ejima K., Kim K.S., Ludema C., Bento A.I., Iwanami S., Fujita Y., Ohashi H., Koizumi Y., Watashi K., Aihara K., Nishiura H., Iwami S.

    Epidemics   35 巻   頁: 100454 - 100454   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Epidemics  

    The incubation period, or the time from infection to symptom onset, of COVID-19 has usually been estimated by using data collected through interviews with cases and their contacts. However, this estimation is influenced by uncertainty in the cases’ recall of exposure time. We propose a novel method that uses viral load data collected over time since hospitalization, hindcasting the timing of infection with a mathematical model for viral dynamics. As an example, we used reported data on viral load for 30 hospitalized patients from multiple countries (Singapore, China, Germany, and Korea) and estimated the incubation period. The median, 2.5, and 97.5 percentiles of the incubation period were 5.85 days (95 % CI: 5.05, 6.77), 2.65 days (2.04, 3.41), and 12.99 days (9.98, 16.79), respectively, which are comparable to the values estimated in previous studies. Using viral load to estimate the incubation period might be a useful approach, especially when it is impractical to directly observe the infection event.

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  19. Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro 査読有り 国際誌

    Shionoya K., Yamasaki M., Iwanami S., Ito Y., Fukushi S., Ohashi H., Saso W., Tanaka T., Aoki S., Kuramochi K., Iwami S., Takahashi Y., Suzuki T., Muramatsu M., Takeda M., Wakita T., Watashi K.

    Frontiers in Microbiology   12 巻   頁: 651403 - 651403   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers in Microbiology  

    Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 1.28 μM, IC90 = 2.31 μM, and IC99 = 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.

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  20. Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment 査読有り 国際誌

    Ohashi H., Watashi K., Saso W., Shionoya K., Iwanami S., Hirokawa T., Shirai T., Kanaya S., Ito Y., Kim K.S., Nomura T., Suzuki T., Nishioka K., Ando S., Ejima K., Koizumi Y., Tanaka T., Aoki S., Kuramochi K., Suzuki T., Hashiguchi T., Maenaka K., Matano T., Muramatsu M., Saijo M., Aihara K., Iwami S., Takeda M., McKeating J.A., Wakita T.

    iScience   24 巻 ( 4 ) 頁: 102367 - 102367   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:iScience  

    Antiviral treatments targeting the coronavirus disease 2019 are urgently required. We screened a panel of already approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new agents having higher antiviral potentials than the drug candidates such as remdesivir and chroloquine in VeroE6/TMPRSS2 cells: the anti-inflammatory drug cepharanthine and human immunodeficiency virus protease inhibitor nelfinavir. Cepharanthine inhibited SARS-CoV-2 entry through the blocking of viral binding to target cells, while nelfinavir suppressed viral replication partly by protease inhibition. Consistent with their different modes of action, synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation was highlighted. Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining cepharanthine/nelfinavir enhanced their predicted efficacy. These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of cepharanthine and nelfinavir.

    DOI: 10.1016/j.isci.2021.102367

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  21. Time variation in the probability of failing to detect a case of polymerase chain reaction testing for SARS-CoV-2 as estimated from a viral dynamics model 査読有り 国際誌

    Ejima K., Kim K.S., Iwanami S., Fujita Y., Li M., Zoh R.S., Aihara K., Miyazaki T., Wakita T., Iwami S.

    Journal of the Royal Society Interface   18 巻 ( 177 ) 頁: 20200947 - 20200947   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of the Royal Society Interface  

    Viral tests including polymerase chain reaction (PCR) tests are recommended to diagnose COVID-19 infection during the acute phase of infection. A test should have high sensitivity; however, the sensitivity of the PCR test is highly influenced by viral load, which changes over time. Because it is difficult to collect data before the onset of symptoms, the current literature on the sensitivity of the PCR test before symptom onset is limited. In this study, we used a viral dynamics model to track the probability of failing to detect a case of PCR testing over time, including the presymptomatic period. The model was parametrized by using longitudinal viral load data collected from 30 hospitalized patients. The probability of failing to detect a case decreased toward symptom onset, and the lowest probability was observed 2 days after symptom onset and increased afterwards. The probability on the day of symptom onset was 1.0% (95% CI: 0.5 to 1.9) and that 2 days before symptom onset was 60.2% (95% CI: 57.1 to 63.2). Our study suggests that the diagnosis of COVID-19 by PCR testing should be done carefully, especially when the test is performed before or way after symptom onset. Further study is needed of patient groups with potentially different viral dynamics, such as asymptomatic cases.

    DOI: 10.1098/rsif.2020.0947

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  22. A quantitative model used to compare withinhost SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2 査読有り

    Kim K.S., Ejima K., Iwanami S., Fujita Y., Ohashi H., Koizumi Y., Asai Y., Nakaoka S., Watashi K., Aihara K., Thompson R.N., Ke R., Perelson A.S., Iwami S.

    PLoS Biology   19 巻 ( 3 )   2021年3月

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    記述言語:日本語   出版者・発行元:PLoS Biology  

    The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2-3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARSCoV- 2 and may be useful for development of antiviral therapies.

    DOI: 10.2110/JSR.2020.113

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  23. Should a viral genome stay in the host cell or leave? A quantitative dynamics study of how hepatitis C virus deals with this dilemma 査読有り 国際誌

    Iwanami S., Kitagawa K., Ohashi H., Asai Y., Shionoya K., Saso W., Nishioka K., Inaba H., Nakaoka S., Wakita T., Diekmann O., Iwami S., Watashi K.

    PLoS Biology   18 巻 ( 7 ) 頁: e3000562   2020年7月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PLoS Biology  

    Virus proliferation involves gene replication inside infected cells and transmission to new target cells. Once positive-strand RNA virus has infected a cell, the viral genome serves as a template for copying (“stay-strategy”) or is packaged into a progeny virion that will be released extracellularly (“leave-strategy”). The balance between genome replication and virion release determines virus production and transmission efficacy. The ensuing trade-off has not yet been well characterized. In this study, we use hepatitis C virus (HCV) as a model system to study the balance of the two strategies. Combining viral infection cell culture assays with mathematical modeling, we characterize the dynamics of two different HCV strains (JFH-1, a clinical isolate, and Jc1-n, a laboratory strain), which have different viral release characteristics. We found that 0.63% and 1.70% of JFH-1 and Jc1-n intracellular viral RNAs, respectively, are used for producing and releasing progeny virions. Analysis of the Malthusian parameter of the HCV genome (i.e., initial proliferation rate) and the number of de novo infections (i.e., initial transmissibility) suggests that the leave-strategy provides a higher level of initial transmission for Jc1-n, whereas, in contrast, the stay-strategy provides a higher initial proliferation rate for JFH-1. Thus, theoretical-experimental analysis of viral dynamics enables us to better understand the proliferation strategies of viruses, which contributes to the efficient control of virus transmission. Ours is the first study to analyze the stay-leave trade-off during the viral life cycle and the significance of the replication-release switching mechanism for viral proliferation.

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  24. Revealing uninfected and infected target cell dynamics from peripheral blood data in highly and less pathogenic simian/human immunodeficiency virus infected Rhesus macaque 査読有り

    Hara A., Iwanami S., Ito Y., Miura T., Nakaoka S., Iwami S.

    Journal of Theoretical Biology   479 巻   頁: 29 - 36   2019年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Theoretical Biology  

    Since chimeric simian and human immunodeficiency viruses (SHIVs) used here, that is, SHIV-#64 and -KS661 utilize both CCR5 and CXCR4 chemokine receptors, they have broad target cell properties. A highly pathogenic SHIV strain, SHIV-KS661, causes an infection that systemically depletes the CD4+ T cells of Rhesus macaques, while a less pathogenic strain, SHIV-#64, does not cause severe symptoms in the macaques. In our previous studies, we established in vitro quantification system for virus infection dynamics, and concluded that SHIV-KS661 effectively produces infectious virions compared with SHIV-#64 in the HSC-F cell culture. However, in vivo dynamics of SHIV infection have not been well understood. To quantify SHIV-#64 and -KS661 infection dynamics in Rhesus macaques, we developed a novel approach and analyzed total CD4+ T cells and viral load in peripheral blood, and reproduced the expected dynamics for the uninfected and infected CD4+ T cells in silico. Using our previous cell culture experimental datasets, we revealed that an infection rate constant is different between SHIV-#64 and -KS661, but the viral production rate and the death rate are similar for the both strains. Thus, here, we assumed these relations in our in vivo data and carried out the data fitting. We performed Bayesian estimation for the whole dataset using MCMC sampling, and simultaneously fitted our novel model to total CD4+ T cells and viral load of SHIV-#64 and -KS661 infection. Our analyses explained that the Malthusian parameter (i.e., fitness of virus infection) and the basic reproduction number (i.e., potential of virus infection) for SHIV-KS661 are significantly higher than those of SHIV-#64. In addition, we demonstrated that the number of uninfected CD4+ T cells in SHIV-KS661 infected Rhesus macaques decreases to the significantly lower value than that before the inoculation several days earlier compared with SHIV-#64 infection. Taken together, the differences between SHIV-#64 and -KS661 infection before the peak viral load might determine the subsequent destiny, that is, whether the systemic CD4+ T cell depletion occurs or the host immune response develop.

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  25. A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture 査読有り

    Iwanami S., Kakizoe Y., Morita S., Miura T., Nakaoka S., Iwami S.

    Theoretical Biology and Medical Modelling   14 巻 ( 1 ) 頁: 9   2017年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Theoretical Biology and Medical Modelling  

    Background: The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains - the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64 - and measured the time-course of experimental data in cell culture. Methods: We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains. Results and conclusions: We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID50, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID50/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture.

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    その他リンク: http://link.springer.com/article/10.1186/s12976-017-0055-8/fulltext.html

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書籍等出版物 1

  1. Quantitative immunology by data analysis using mathematical models

    Iwanami S., Iwami S.

    Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics  2018年1月  ( ISBN:9780128114148

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    記述言語:日本語

    Mathematical models have been widely used for analysis of experimental data in immunology, which can describe the interactions among cells or antigens. Many mathematical modeling studies have provided novel insights into immune systems. These researches adopt a generalized mathematical model based on population dynamics, which is frequently used in ecology or demography. By discussing several studies of cell differentiation, lymphocyte turnover and virus dynamics, we demonstrate the applicability of the generalized mathematical model to immunology data analysis.

    DOI: 10.1016/B978-0-12-809633-8.20250-1

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MISC 7

  1. 特集 未病の科学 Ⅰ.未病の数理研究 多階層ウイルス感染動態の数理モデリングとデータサイエンス

    岩波 翔也, 岩見 真吾  

    生体の科学74 巻 ( 2 ) 頁: 112 - 117   2023年4月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.2425201654

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  2. ウイルス感染動態に基づいた抗ウイルス薬の評価と臨床試験設計の検討

    岩波翔也  

    実験医学40 巻 ( 13 ) 頁: 2115 - 2121   2022年8月

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    担当区分:筆頭著者, 最終著者, 責任著者   記述言語:日本語  

  3. 新型コロナウイルス感染症研究のデジタルトランスフォーメーション

    朴炯基, 禹周賢, 岩波翔也, 岩見真吾  

    ウイルス72 巻 ( 1 ) 頁: 39 - 46   2022年6月

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    記述言語:日本語  

  4. 疾患の数理モデリングと定量的データ解析

    数理科学699 巻   頁: 16 - 22   2021年9月

  5. 新型コロナウイルスの生体内感染動態の定量化とその応用/数理科学で挑む新型コロナウイルス感染症治療の確立

    岩波翔也, キム・クァンス, 藤田泰久, 江島啓介, 岩見真吾  

    数学セミナー707 巻   頁: 33 - 39   2020年9月

  6. 骨髄球バイパスを含む造血システムの数理モデルを用いた1細胞移植実験のデータ解析 (第14回生物数学の理論とその応用 : 構造化個体群ダイナミクスとその応用)

    岩波 翔也, 山本 玲, 岩見 真吾, 波江野 洋  

    数理解析研究所講究録 ( 2087 ) 頁: 77 - 85   2018年8月

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    記述言語:日本語   出版者・発行元:京都大学数理解析研究所  

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    その他リンク: http://hdl.handle.net/2433/251581

  7. 骨髄球バイパスを含む造血システムの数理モデル (第13回生物数学の理論とその応用 : 連続および離散モデルのモデリングと解析)

    岩波 翔也, 山本 玲, 岩見 真吾, 波江野 洋  

    数理解析研究所講究録 ( 2043 ) 頁: 102 - 108   2017年9月

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    記述言語:日本語   出版者・発行元:京都大学数理解析研究所  

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    その他リンク: http://hdl.handle.net/2433/236964

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共同研究・競争的資金等の研究課題 3

  1. 糸状菌真菌症に対する疫学調査及び革新的診断法と治療法の研究開発

    研究課題番号:22fk0108544  2023年7月 - 2024年3月

    新興・再興感染症に対する革新的医薬品等開発推進研究事業 

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    担当区分:研究分担者  資金種別:競争的資金

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  2. 新規抗サル痘ウイルス化合物の最適化とドラッグリポジショニングによる治療法の開発

    研究課題番号:JP21fk0108421  2022年10月 - 2023年3月

    新興・再興感染症に対する革新的医薬品等開発推進研究事業 

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    担当区分:研究分担者  資金種別:競争的資金

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  3. 数理科学が推進するパンデミックナレッジ基盤の構築

    研究課題番号:JPMJPR21R3  2021年10月 - 2025年3月

    戦略的創造研究推進事業(さきがけ)「パンデミックに対してレジリエントな社会・技術基盤の構築」領域 

    岩波翔也

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    担当区分:研究代表者  資金種別:競争的資金

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科研費 2

  1. 細胞群動態の変容を捉える多階層データ解析理論の構築

    研究課題/研究課題番号:22K15073  2022年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    岩波 翔也

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    担当区分:研究代表者 

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    細胞集団の数の変化を捉えるための個体群動態を土台として、個々の細胞の分化と頻度の少ない小さなイベントが与える影響を補足するために、確率論的なモデルを用いる。また、確率モデル中で計算される各細胞 個体には、遺伝子配列情報を特性として内包させ、生成した疑似配列の系統樹を構築する。 そして、統計学・集団遺伝学・進化生態学の手法を用いて、細胞集団全体の挙動と配列情報 から得られる指標を比較する。同様の手法を実験から得られるデータにも適用し、細胞群の 変化を説明する指標を導出する。

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  2. 組織維持を担う細胞群個体群動態の理解と定量的データ解析

    研究課題/研究課題番号:19J12319  2019年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    岩波 翔也, 岩波 翔也

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    担当区分:その他 

    生体内では、細胞群が相互に影響を与え合いながら組織の恒常性を維持している。ここでは、幹細胞が維持する組織として老化の研究が盛んに行われている造血組織と、細胞が組織を形成と破壊のバランスを取りながら維持している骨組織に着目した。
    造血幹細胞は全ての血液細胞と免疫細胞に分化する能力を持ち、生涯にわたって造血組織を維持すると考えられている。また、造血幹細胞の分化機構について、様々な研究結果から複数のモデルが提唱されている。さらに、加齢による造血幹細胞の能力の変化が、造血組織の老化を引き起こすという研究成果が報告されている。造血幹細胞が造血組織を維持し、老化するメカニズムを解明するために、造血幹細胞分化を記述する数理モデルを開発した。この数理モデルを用いて、若齢マウスと老齢マウスから取得された造血幹細胞を移植したときの末梢血中での各細胞系統の変動を解析した。このとき、非線形混合効果モデルの手法を取り入れ、マウスでの移植実験のデータのばらつきを統計的に扱うことが可能な解析手法を構築した。若齢マウスと老齢マウスの造血幹細胞の能力を比較し、老化に伴って骨髄球の産生が多くなることを説明した。今後は、造血幹細胞分化の確率シミュレータを開発し、細胞の分化と組織の維持の関係性の定性的・定量的な解釈を目指す。
    骨組織は骨芽細胞と破骨細胞が相互に作用し合うことで、骨形成と骨吸収のバランスをとりながら維持され、一般に、加齢と共に骨量が減少する。また、重力変化や閉経などの摂動によって骨量が変化することが示唆されている。ここでは、マウスで取得された骨代謝マーカーと骨量変動の長期の時系列データと、人工的に重力をかけられたマウスのデータを同時に解析し、骨代謝マーカーの変動から骨量の変動を説明することに成功した。今後は、他の摂動実験を説明しうる数理モデルを開発していく。

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