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Molecular backgrounds of transplacental Zika fever infection.

Research Project

Project/Area Number 17H04341
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNihon University

Principal Investigator

HAYAKAWA Satoshi  日本大学, 医学部, 教授 (30238084)

Co-Investigator(Kenkyū-buntansha) 相澤 志保子  日本大学, 医学部, 准教授 (30513858)
川名 敬  日本大学, 医学部, 教授 (60311627)
森岡 一朗  日本大学, 医学部, 教授 (80437467)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywordsジカ熱 / 垂直感染 / 胎盤関門 / 歯周病 / 絨毛羊膜炎 / 血管内皮 / TGF-β / 慢性炎症 / 母子感染 / 絨毛細胞 / 子宮内細菌叢 / 新型コロナウイルス / ジカウイルス / 経胎盤感染 / マイクロバイオーム / 子宮内フローラ / ウイルス垂直感染 / 口腔細菌 / 胎盤マイクロバイオーム / TORCH症候群
Outline of Final Research Achievements

Zika fever causes congenital disorders including microcephaly. However, not all pregnant women develop intrauterine infections. This fact suggests the presence of a placental barrier. Periodontal disease and chorioamnionitis are considered to be risks for vertical transmission but the mechanism is so far unknown. We infected various trophoblast cell lines with Zika virus and examined their susceptibility. Though the natural virus replication and release were limited, TGF-β strongly enhanced infectivity, with enhanced expression of Tyro3 and AXL (the receptor for ZIKV) as a possible mechanism. The increased susceptibility of the villi themselves, in addition to exposure to highly susceptible Hofbauer cells and vascular endothelial cells due to disruption of the villi structure in pathological conditions such as periodontal disease and chorioamnionitis, was assumed to be a factor increasing the risk of vertical infection.

Academic Significance and Societal Importance of the Research Achievements

胎盤はジカウイルスに感染するが複製は制御されている。言い換えると、胎盤にはウイルスが胎児に侵入しないような防御機構が存在する。従って、妊婦は感染を避けることは極めて重要であるが、感染したからといって過度に心配する必要はない。しかし歯周病や絨毛羊膜炎などの炎症でバリアが破綻すると子宮内感染を来す。我々は感受性増強にはTGF-βが重要であることを証明したが、このメカニズムは風疹やCOVID-19でも同様である。妊婦と妊娠を希望する女性は慢性炎症を避けることが重要といえる。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (51 results)

All 2022 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (10 results) Journal Article (28 results) (of which Int'l Joint Research: 14 results,  Peer Reviewed: 27 results,  Open Access: 6 results) Presentation (4 results) (of which Invited: 4 results) Book (8 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Wayne State University/City of Hope Research Institute(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Hang Yang University(韓国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Cheng Mai University(タイ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] チェンマイ大学(タイ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Wayne state 大学/City of Hope 研究所(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ハンヤン大学(韓国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] サンパウロ国立大学(ブラジル)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] City of Hope Research Institute(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] CNRS(フランス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Chang Mai University(タイ)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] TGF-β1 Promotes Zika Virus Infection in Immortalized Human First-Trimester Trophoblasts via the Smad Pathway2022

    • Author(s)
      Trinh QD, Pham NTK, Takada K, Takano C, Komine-Aizawa S, Hayakawa S.
    • Journal Title

      Cells

      Volume: 27 Issue: 19 Pages: 3026-3026

    • DOI

      10.3390/cells11193026

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-SARS-CoV-2 vaccination strategy for pregnant women in Japan.2021

    • Author(s)
      Hayakawa S, Komine-Aizawa S, Takada K, Kimura T, Yamada H.
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 47 Issue: 6 Pages: 14748-14748

    • DOI

      10.1111/jog.14748

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Epithelial-to-Mesenchymal Transition-Like Process Induced by TGF-β1 Enhances Rubella Virus Binding and Infection in A549 Cells via the Smad Pathway2021

    • Author(s)
      Pham Thi Kim Ngan、Trinh Duy Quang、Takada Kazuhide、Takano Chika、Sasano Mari、Okitsu Shoko、Ushijima Hiroshi、Komine-Aizawa Shihoko、Hayakawa Satoshi
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 3 Pages: 662-662

    • DOI

      10.3390/microorganisms9030662

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Placental barrier against COVID-19.2020

    • Author(s)
      Komine-Aizawa S, Takada K, Hayakawa S.
    • Journal Title

      Placenta. Sep 15;99:45-49. doi:

      Volume: 99 Pages: 45-49

    • DOI

      10.1016/j.placenta.2020.07.022

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Covid-19 pandemic and pregnancy.2020

    • Author(s)
      Hayakawa S, Komine-Aizawa S, Mor GG.
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 46 Issue: 10 Pages: 1958-1966

    • DOI

      10.1111/jog.14384

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cow milk exosomes activate NK cells and γδT cells in human PBMCs in?vitro2020

    • Author(s)
      Shihoko Komine-Aizawa、Shun Ito、Shu Aizawa、Takahiro Namiki、Satoshi Hayakawa
    • Journal Title

      Immunological Medicine

      Volume: 43 Issue: 4 Pages: 161-170

    • DOI

      10.1080/25785826.2020.1791400

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible Importance of Carcasses for Ebolavirus Persistence in the Ecosystem.2020

    • Author(s)
      Namiki T, Hayakawa S.
    • Journal Title

      Med Hypotheses.

      Volume: 138 Pages: 109595-109595

    • DOI

      10.1016/j.mehy.2020.109595

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and Accurate Species Identification of Mitis Group Streptococci Using the MinION Nanopore Sequencer.2020

    • Author(s)
      Imai K, Nemoto R, Koda M, Tarumoto N, Sakai J, Kawamura T, Ikebuchi K, Mitsutake K, Murakami T, Maesaki S, Fujiwara T, Hayakawa S, Hoshino T, Seki M, Maeda T.
    • Journal Title

      Front Cell Infect Microbiol

      Volume: 11 Pages: 1-11

    • DOI

      10.3389/fcimb.2020.00011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular detection of enteric viruses in the stool samples of children without diarrhea in Bangladesh.2019

    • Author(s)
      Okitsu S, Khamrin P, Takanashi S, Thongprachum A, Hoque SA, Takeuchi H, Khan MA, Hasan SMT, Iwata T, Shimizu H, Jimba M, Hayakawa S, Maneekarn N, Ushijima H.
    • Journal Title

      Infect Genet Evol

      Volume: 77 Pages: 104055-104055

    • DOI

      10.1016/j.meegid.2019.104055

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Occurrence of noroviruses in recycled water and sewage sludge: emergence of recombinant norovirus strains.2019

    • Author(s)
      Kittigul L, Rupprom K, Che-Arsae M1, Pombubpa K, Thongprachum A, Hayakawa S, Ushijima H
    • Journal Title

      J Appl Microbiol

      Volume: 126 Issue: 4 Pages: 1290-1301

    • DOI

      10.1111/jam.14201

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Relationship Between the Fecal Microbiota and Depression and Anxiety in Pediatric Patients With Orthostatic Intolerance.2019

    • Author(s)
      Ishii W, Komine-Aizawa S, Takano C, Fujita Y, Morioka I, Hayakawa S.
    • Journal Title

      Prim Care Companion CNS Disord.

      Volume: 21 Issue: 2

    • DOI

      10.4088/pcc.18m02401

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MHC-restricted Ag85B-specific CD8+ T cells are enhanced by recombinant BCG prime and DNA boost immunization in mice2019

    • Author(s)
      Komine-Aizawa S, Jiang J, Mizuno S, Hayakawa S, Matsuo K, Boyd LF, Margulies DH, Honda M.
    • Journal Title

      .Eur J Immunol.

      Volume: 49 Issue: 9 Pages: 1399-1414

    • DOI

      10.1002/eji.201847988

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diversity of human parechovirus in infants and children with acute gastroenteritis in Japan during 2014?20162019

    • Author(s)
      Pham Ngan Thi Kim、Thongprachum Aksara、Shimizu Yuko、Trinh Quang Duy、Okitsu Shoko、Komine-Aizawa Shihoko、Shimizu Hiroyuki、Hayakawa Satoshi、Ushijima Hiroshi
    • Journal Title

      Infection, Genetics and Evolution

      Volume: 75 Pages: 104001-104001

    • DOI

      10.1016/j.meegid.2019.104001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Determining effectiveness of rotavirus vaccine by immunochromatography and reverse transcriptase polymerase chain reaction: A comparison.2019

    • Author(s)
      Hoque SA, Iizuka I, Kobayashi M, Takanashi S, Anwar KS, Islam MT, Hoque SA, Khamrin P, Okitsu S, Hayakawa S, Ushijima H.
    • Journal Title

      Vaccine

      Volume: 39 Issue: 39 Pages: 5886-5890

    • DOI

      10.1016/j.vaccine.2019.07.091

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular serotype-specific identification of Streptococcus pneumoniae using loop-mediated isothermal amplification2019

    • Author(s)
      Takano C, Kuramochi Y, Seki M, Kim DW, Omagari D, Sasano M, Chang B, Ohnishi M, Kim EJ, Fuwa K, Kilgore PE, Hoshino T, Hayakawa S. .
    • Journal Title

      Sci Rep. 2019

      Volume: 9 Issue: 1 Pages: 19823-19823

    • DOI

      10.1038/s41598-019-56225-0

    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Development of a Novel Loop-Mediated Isothermal Amplification Method to Detect Guiana Extended-Spectrum (GES) β-Lactamase Genes in Pseudomonas aeruginosa.2019

    • Author(s)
      Takano C, Seki M, Kim DW, Gardner H, McLaughlin RE, Kilgore PE, Kumasaka K, Hayakawa S.
    • Journal Title

      Front Microbiol.

      Volume: 10 Pages: 25-25

    • DOI

      10.3389/fmicb.2019.00025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Alarming Situation of Spreading Enteric Viruses Through Sewage Water in Dhaka City: Molecular Epidemiological Evidences.2019

    • Author(s)
      Ariful Hoque SA, Thongprachum A, Takanashi S, Mostafa SM, Saito H, Anwar KS, Nomura A, Hoque A, Begum R, Sultana UN, Hossain T, Khamrin P, Okitsu S, Hayakawa S, Ushijima H
    • Journal Title

      Food Environ Virol

      Volume: 11 Issue: 1 Pages: 65-75

    • DOI

      10.1007/s12560-018-09363-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Periodontal diseases and adverse pregnancy outcomes.2019

    • Author(s)
      Komine-Aizawa S, Aizawa S, Hayakawa S
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 45 Issue: 1 Pages: 5-12

    • DOI

      10.1111/jog.13782

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lactobacillus crispatus accelerates re-epithelialization in vaginal epithelial cell line MS74.2018

    • Author(s)
      Takada K, Komine-Aizawa S, Kuramochi T, Ito S, Trinh QD, Pham NTK, Sasano M, Hayakawa S.
    • Journal Title

      Am J Reprod Immunol.

      Volume: 80 Issue: 3

    • DOI

      10.1111/aji.13027

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Synergistic induction of interferon-γ by interleukin-2, interleukin-12 and poly(I:C) in a human natural killer cell line2018

    • Author(s)
      Majima-Horiuchi H, Komine-Aizawa S, Karasaki-Suzuki M, Izumi Y, Aizawa S, Hayakawa S. .
    • Journal Title

      Immunol Med.

      Volume: 41 Issue: 3 Pages: 136-141

    • DOI

      10.1080/25785826.2018.1531193

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and simple detection of Ureaplasma species from vaginal swab samples using a loop-mediated isothermal amplification method.2018

    • Author(s)
      Fuwa K, Seki M, Hirata Y, Yanagihara I, Nakura Y, Takano C, Kuroda K, Hayakawa S.
    • Journal Title

      Am J Reprod Immunol.

      Volume: 79 Issue: 1 Pages: 1-8

    • DOI

      10.1111/aji.12771

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent isolation of extended-spectrum beta-lactamase-producing bacteria from fecal samples of individuals with severe motor and intellectual disabilities.2018

    • Author(s)
      Takano C, Seki M, Shiihara H, Komine-Aizawa S, Kuroda K, Takahashi S, Ushijima H, Hayakawa S.
    • Journal Title

      J Infect Chemother.

      Volume: 24 Issue: 3 Pages: 182-187

    • DOI

      10.1016/j.jiac.2017.10.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loop-Mediated Isothermal Amplification Methods for Diagnosis of Bacterial Meningitis.2018

    • Author(s)
      Seki M, Kilgore PE, Kim EJ, Ohnishi M, Hayakawa S, Kim DW.
    • Journal Title

      Front Pediatr.

      Volume: 6 Pages: 1-6

    • DOI

      10.3389/fped.2018.00057

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of rotavirus vaccination on an emerging G8P[8] rotavirus strain causing an outbreak in central Japan2018

    • Author(s)
      Hoque SA, Kobayashi M, Takanashi S, Anwar KS, Watanabe T, Khamrin P, Okitsu S, Hayakawa S, Ushijima H. Vaccine.
    • Journal Title

      Vaccine

      Volume: 36 Pages: 43-49

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Myelin oligodendrocyte glycoprotein-independent rubella infection of keratinocytes and resistance of first-trimester trophoblast cells to rubella virus in vitro2018

    • Author(s)
      Quang Duy Trinh、Ngan Thi Kim Pham、Kazuhide Takada、Shihoko Komine-Aizawa、Satoshi Hayakawa
    • Journal Title

      Viruses

      Volume: 10 Issue: 1 Pages: 23-23

    • DOI

      10.3390/v10010023

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Poly I:C induces collective migration of HaCaT keratinocytes via IL-8.2017

    • Author(s)
      Takada K, Komine-Aizawa S, Hirohata N, Trinh QD, Nishina A, Kimura H, Hayakawa S.
    • Journal Title

      BMC Immunol.

      Volume: 18 Issue: 1 Pages: 19-19

    • DOI

      10.1186/s12865-017-0202-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Porphyromonas gingivalis Suppresses Trophoblast Invasion by Soluble Factors.2017

    • Author(s)
      Hirohata N, Komine-Aizawa S, Tamura M, Ochiai K, Sugitani M, Hayakawa S. .
    • Journal Title

      J Periodontol

      Volume: 88 Issue: 12 Pages: 1366-1373

    • DOI

      10.1902/jop.2017.170193

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multiplex RT-PCR for rapid detection of viruses commonly causing diarrhea in pediatric patients2017

    • Author(s)
      Thongprachum A, Khamrin P, Thi Kim Pham N, Takanashi S, Okitsu S, Shimizu H, Maneekarn N, Hayakawa S, Ushijima H
    • Journal Title

      J Med Virol

      Volume: 89 Issue: 5 Pages: 818-824

    • DOI

      10.1002/jmv.24711

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 生殖生物学から考える細菌叢2021

    • Author(s)
      早川 智
    • Organizer
      第5回ART Clinical Research Conference
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 腸管と女性生殖器のマイクロビオータ:隣どうしの誼 腸内フローラと炎症 ~共生微生物との関わり合い~2021

    • Author(s)
      早川 智
    • Organizer
      第29回腸内フローラシンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 教育講演34 医学史から見た感染症2019

    • Author(s)
      早川 智
    • Organizer
      第93回日本感染症総会・学術講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 胎盤幹細胞に対する 風疹感染系の試み2017

    • Author(s)
      早川 智
    • Organizer
      第25回日本胎盤学会ワークショップ
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] 標準微生物学 第14版2021

    • Author(s)
      神谷 茂  錫谷 達夫  松本 哲哉 編 早川 智(分担執筆)
    • Total Pages
      704
    • Publisher
      医学書院
    • ISBN
      9784260043311
    • Related Report
      2020 Annual Research Report
  • [Book] 不育症2021

    • Author(s)
      竹下俊行、藤井知行、山田秀人 編 早川 智(分担執筆)
    • Total Pages
      248
    • Publisher
      メジカルビュー社
    • ISBN
      9784758319966
    • Related Report
      2020 Annual Research Report
  • [Book] 産科の感染防御ガイド2020

    • Author(s)
      日本産婦人科医会・日本母体救命システム普及協議会 (監修) 早川 智(分担執筆)
    • Total Pages
      176
    • Publisher
      MC メデイカ出版
    • Related Report
      2020 Annual Research Report
  • [Book] 今日の診断指針 第8版 (母子感染)2020

    • Author(s)
      早川 智(分担執筆)永井良三 総編集
    • Total Pages
      2079
    • Publisher
      医学書院
    • ISBN
      9784260038089
    • Related Report
      2019 Annual Research Report
  • [Book] 実践 臨床生殖免疫学2018

    • Author(s)
      編者 柴原浩章   早川 智 (共著)担当範囲I総論 3.感染免疫、II各論 5.妊娠と免疫- 8 歯周病、6.感染症と免疫-2-妊娠と感染症⑧HIV・AIDS
    • Total Pages
      730
    • Publisher
      中外医学社
    • ISBN
      9784498060883
    • Related Report
      2018 Annual Research Report
  • [Book] 産婦人科感染症マニュアル2018

    • Author(s)
      早川 智 (分担執筆) 日本産婦人科感染症学会 編
    • Total Pages
      344
    • Publisher
      金原出版
    • ISBN
      4307301358
    • Related Report
      2017 Annual Research Report
  • [Book] 標準微生物学 第13版2018

    • Author(s)
      早川 智 (分担執筆) 中込 治 神谷茂 編
    • Total Pages
      663
    • Publisher
      医学書院
    • ISBN
      4260034561
    • Related Report
      2017 Annual Research Report
  • [Book] 1336専門家による 私の治療 2017-18年度版2017

    • Author(s)
      早川 智 (分担執筆) 猿田 享男 (監修), 北村 惣一郎 (監修)
    • Total Pages
      1776
    • Publisher
      日本医事新報社
    • ISBN
      9784784946501
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 淋菌のDNAジャイレースのサブユニットAの83番目のアミノ酸をコードする塩基配列における変異検出プライマーセット2019

    • Inventor(s)
      早川 智 他
    • Industrial Property Rights Holder
      早川 智 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2023-01-30  

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