Identification of amino acids critical for cell entry of ZIKV and elucidation of exacerbation mechanisms of neurological disorder associated with ZIKV infection

• Project/Area Number: 20K18482
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Oita University
• Principal Investigator: Kamiyama Naganori 大分大学, 医学部, 准教授 (50756830)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ジカウイルス / 多発性硬化症 / EAE / ケモカイン / SRIPs / 神経変性疾患

Outline of Research at the Start

ジカ熱を引き起こすジカウイルスは、アフリカで単離され、アジアを経由する間に変異が起こり世界中に広がった。近年、ブラジルやプエルトリコにおけるジカウイルスの大流行では小頭症やギランバレー症候群などの神経変性疾患への関与が問題となった。
ジカウイルスはアフリカ株とアジア株に分類される。我々はアフリカ株が培養細胞への高い侵入能を有し、マウスの神経変性疾患を増悪させることを見出した。 本研究では両株間のアミノ酸配列のわずかな違いを手掛かりに、ジカウイルスの細胞侵入能を規定するアミノ酸を同定する。さらに、ジカウイルスが免疫応答に及ぼす影響に着目して神経変性疾患を増悪させる分子機構を解明する。

Outline of Final Research Achievements

Genetically, the lineage of ZIKV is classified broadly into African and Asian strain. We demonstrate that SRIPs of African strain show higher cell entry ability than that of Asian strain. Furthermore, our study identified 1 amino acid of African strain envelope protein as the key residue, which is required for strong cell entry ability.
We demonstrated that ZIKV infection exacerbated EAE, the most common animal model for multiple sclerosis. ZIKV infection accelerated pathogenic Th17 cell infiltration into the central nervous system by upregulating the chemokines for the migration of the cell.

Academic Significance and Societal Importance of the Research Achievements

近年、プエルトリコやブラジルなどでジカウイルス感染症の大流行がおこり、それぞれギラン・バレー症候群、小頭症などの神経変性疾患との関連が報告され、国際的な問題となった。しかしながら、現在においても有効な治療薬やワクチンが存在しない。
我々はジカウイルスの宿主細胞に対する侵入能を規定するエンベロープタンパクのアミノ酸を同定した。さらに、ジカウイルス感染が多発性硬化症のマウスモデルEAEの病態を増悪化させることを見出し、その増悪化メカニズムを明らかにした。これら知見はジカウイルス感染の予防薬や感染に伴う神経変性疾患の新たな治療法の開発に繋がることが期待される。

Research Products

• [Journal Article] Acute Cholecystitis Associated with Eosinophilic Granulomatosis with Polyangiitis That Responded to Glucocorticoid Therapy (2023)
  • Author(s): Ozaka Sotaro、Kodera Takamoto、Tsutsumi Koshiro、Fukuda Masahide、Iwao Masao、Hirashita Yuka、Takahashi Haruhiko、Fukuda Kensuke、Okamoto Kazuhisa、Arakawa Mie、Ogawa Ryo、Endo Mizuki、Mizukami Kazuhiro、Okimoto Tadayoshi、Kamiyama Naganori、Kodama Masaaki、Kobayashi Takashi、Murakami Kazunari
  • Journal Title: Internal Medicine Volume: 62 Issue: 10 Pages: 1501-1506
  • DOI: 10.2169/internalmedicine.0437-22
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2023-05-15
  • Peer Reviewed / Open Access
• [Journal Article] GM-CSF-producing CCR2+ CCR6+ Th17 cells are pathogenic in dextran sodium sulfate-induced colitis model in mice (2023)
  • Author(s): Ariki Shimpei、Ozaka Sotaro、Sachi Nozomi、Chalalai Thanyakorn、Soga Yasuhiro、Fukuda Chiaki、Kagoshima Yomei、Ekronarongchai Supanuch、Mizukami Kazuhiro、Kamiyama Naganori、Murakami Kazunari、Kobayashi Takashi
  • Journal Title: Genes to Cells Volume: 28 Issue: 4 Pages: 267-276
  • DOI: 10.1111/gtc.13008
  • Peer Reviewed / Open Access
• [Journal Article] CCL20/CCR6 chemokine signaling is not essential for pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis (2023)
  • Author(s): Sachi Nozomi、Kamiyama Naganori、Saechue Benjawan、Ozaka Sotaro、Dewayani Astri、Ariki Shimpei、Chalalai Thanyakorn、Soga Yasuhiro、Fukuda Chiaki、Kagoshima Yomei、Ekronarongchai Supanuch、Kobayashi Takashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 641 Pages: 123-131
  • DOI: 10.1016/j.bbrc.2022.11.088
  • Peer Reviewed
• [Journal Article] Saireito, a Japanese herbal medicine, alleviates leaky gut associated with antibiotic-induced dysbiosis in mice (2022)
  • Author(s): Ozaka S、Sonoda A、Ariki S、Minata M、Kamiyama N、Hidano S、Sachi N、Ito K、Kudo Y、Dewayani A、Chalalai T、Ozaki T、Soga Y、Fukuda C、Mizukami K、Ishizawa S、Nishiyama M、Fujitsuka N、Mogami S、Kubota K、Murakami K、Kobayashi T
  • Journal Title: PLOS ONE Volume: 17 Issue: 6 Pages: e0269698-e0269698
  • DOI: 10.1371/journal.pone.0269698
  • Peer Reviewed / Open Access
• [Journal Article] TRAF6 signaling pathway in T cells regulates anti-tumor immunity through the activation of tumor specific Th9 cells and CTLs (2022)
  • Author(s): Dewayani Astri、Kamiyama Naganori、Sachi Nozomi、Ozaka Sotaro、Saechue Benjawan、Ariki Shimpei、Goto Mizuki、Chalalai Thanyakorn、Soga Yasuhiro、Fukuda Chiaki、Kagoshima Yomei、Maekawa Yoichi、Kobayashi Takashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 613 Pages: 26-33
  • DOI: 10.1016/j.bbrc.2022.04.125
  • Peer Reviewed
• [Journal Article] Comprehensive lipidomics of lupus-prone mice using LC-MS/MS identifies the reduction of palmitoylethanolamide that suppresses TLR9-mediated inflammation. (2022)
  • Author(s): Ozaki T, Kamiyama N, Saechue B, Soga Y, Gotoh R, Nakayama T, Fukuda C, Dewayani A, Chalalai T, Ariki S, Ozaka S, Sonoda A, Hirose H, Gendo Y, Noguchi K, Sachi N, Hidano S, Maeshima K, Gotoh K, Masaki T, Ishii K, Osada Y, Shibata H, Kobayashi T
  • Journal Title: Genes Cells. Volume: 27 Issue: 7 Pages: 493-504
  • DOI: 10.1111/gtc.12944
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of the Prevalence and Species of <i>Anisakis</i> nematode in Sekisaba, <i>Scomber japonicus</i> Caught in Coastal Waters off Saganoseki, Oita in Japan (2021)
  • Author(s): Hidano Shinya、Mizukami Kazuhiro、Yahiro Takaaki、Shirakami Kohei、Ito Hideyuki、Ozaka Sotaro、Ariki Shimpei、Saechue Benjawan、Dewayani Astri、Chalalai Thanyakorn、Soga Yasuhiro、Goto Mizuki、Sonoda Akira、Ozaki Takashi、Sachi Nozomi、Kamiyama Naganori、Nishizono Akira、Murakami Kazunari、Kobayashi Takashi
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 74 Issue: 5 Pages: 387-391
  • DOI: 10.7883/yoken.JJID.2020.859
  • NAID: 130008090913
  • ISSN: 1344-6304, 1884-2836
  • Year and Date: 2021-09-30
  • Peer Reviewed / Open Access
• [Journal Article] Protease inhibitory activity of secretory leukocyte protease inhibitor ameliorates murine experimental colitis by protecting the intestinal epithelial barrier (2021)
  • Author(s): Ozaka S, Sonoda A, Ariki S, Kamiyama N, Hidano S, Sachi N, Ito K, Kudo Y, Minata M, Saechue B, Dewayani A, Chalalai T, Soga Y, Takahashi Y, Fukuda C, Mizukami K, Okumura R, Kayama H, Murakami K, Takeda K, Kobayashi T.
  • Journal Title: Genes to Cells Volume: 26 Issue: 10 Pages: 807-822
  • DOI: 10.1111/gtc.12888
  • Peer Reviewed / Open Access
• [Journal Article] Development of a portable reverse transcription loop‐mediated isothermal amplification system to detect the E1 region of Chikungunya virus in a cost‐effective manner (2020)
  • Author(s): Saechue Benjawan、Kamiyama Naganori、Fukuda Chiaki、Watanabe Kei、Soga Yasuhiro、Goto Mizuki、Dewayani Astri、Ariki Shimpei、Hirose Haruna、Ozaka Sotaro、Sachi Nozomi、Hidano Shinya、Shirin Tahmina、Mondal Dinesh、Murakami Kazunari、Kobayashi Takashi
  • Journal Title: Genes to Cells Volume: 9 Issue: 9 Pages: 615-625
  • DOI: 10.1111/gtc.12797
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Functional analysis of chemokine receptor CCR2 in a murine congenital toxoplasmosis model (2023)
  • Author(s): Naganori Kamiyama, Nozomi Sachi, Sotaro Ozaka, Shimpei Ariki, Thanyakorn Chalalai, Yasuhiro Soga, Chiaki Fukuda, Yomei Kagoshima, Supanuch Ekronarongchai, Masahiro Yamamoto, Takashi Kobayashi
  • Organizer: 第15回寄生虫感染免疫研究会
• [Presentation] Zika virus induces pathogenic T cell-attracting chemokines in the central nervous system and exacerbates experimental autoimmune encephalomyelitis (2022)
  • Author(s): Naganori Kamiyama, Thanyakorn Chalalai, Sotaro Ozaka, Shimpei Ariki, Yomei Kagoshima, Nozomi Sachi, Takashi Kobayashi
  • Organizer: 第51回日本免疫学会学術集会
• [Presentation] ケモカイン受容体 CCR2 のトキソプラズマ垂直感染に対する機能 (2022)
  • Author(s): 神山 長慶, THANYAKORN CHALALAI, 佐知 望美, 小坂 聡太郎, 有木 晋平, 曽我 泰裕, 鹿子嶋 洋明, SUPANUCH EKRONARONGCHAI, 小林 隆志
  • Organizer: 第74回 日本寄生虫学会 南日本支部大会
• [Presentation] Zika virus (ZIKV) induces pathogenic T cells-attracting chemokines in a TRAF6 signaling-dependent manner in astrocyte, and exacerbates EAE (2021)
  • Author(s): Naganori Kamiyama
  • Organizer: Joint Symposium & Workshop: Uniersitas AIRLANGGA and OITA University
  • Int'l Joint Research
• [Presentation] Zika virus infection exacerbates Experimental Autoimmune Encephalomyelitis (2021)
  • Author(s): Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Chalalai Thanyakorn, Sotaro Ozaka, Shimpei Ariki, Chiaki Fukuda, Yasuhiro Soga, Mizuki Minata, Nozomi Sachi, Shinya Hidano, Takashi Kobayashi
  • Organizer: International Meeting_the 3rd Chulalongkorn-Oita University Joint Mini-Symposium
  • Int'l Joint Research
• [Presentation] Zika virus induces Th17 cell-attracting chemokines in the central nervous system and exacerbates neurological disorders (2021)
  • Author(s): Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Chalalai Thanyakorn, Sotaro Ozaka, Shimpei Ariki, Chiaki Fukuda, Yasuhiro Soga, Mizuki Minata, Nozomi Sachi, Shinya Hidano, Takashi Kobayashi
  • Organizer: 第44回日本分子生物学会年会
• [Presentation] Zika virus induces Th17 cell-attracting chemokines in the central nervous system and exacerbates experimental autoimmune encephalomyelitis (2021)
  • Author(s): Naganori Kamiyama, Benjawan Saechue, Astri Dewayan, Thanyakorn Chalalai, Yasuhiro Soga, Chiaki Fukuda, Sotaro Ozaka, Shimpei Ariki, Nozomi Sachi, Shinya Hidano, Takashi Kobayashi
  • Organizer: 第14回寄生虫感染免疫研究会
• [Presentation] DSS腸炎モデルを用いたSLPIの結腸における生理的機能の解析 (2020)
  • Author(s): 小坂聡太郎, 有木晋平, 園田光, 神山長慶, 飛彈野真也, 水上一弘, 小林隆志, 村上和成
  • Organizer: 第28回日本消化器関連学会週間(JDDW) 第62回日本消化器病学会大会
• [Presentation] TRAF6 Signaling in Th9 cells Regulates Anti-Tumor Immune Response (2020)
  • Author(s): Astri Dewayani, Naganori Kamiyama, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shimpei Ariki, Benjawan Saechue, Mizuki Goto, Yasuhiro Soga, Thanyakorn Chalalai, Takashi Kobayashi
  • Organizer: 第43回日本分子生物学会年会
• [Presentation] TRAF6 promotes the migration of Th17 cells into the CNS by regulating CCR6 expression in experimental autoimmune encephalomyelitis mice (2020)
  • Author(s): Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Chalalai Thanyakorn, Sotaro Ozaka, Shinpei Ariki, Yasuhiro Soga, Mizuki Goto, Nozomi Sachi, Shinya Hidano, Takashi Kobayashi
  • Organizer: 第43回日本分子生物学会年会