| Project/Area Number |
18K07088
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
川合 覚 獨協医科大学, 医学部, 教授 (70275733)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | サルマラリア / 感染赤血球 / 接着現象 / SICAvar / トランスクリプトーム / サルマラリア原虫 / Plasmodium knowlesi / 人獣共通感染症 / HUVEC |
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| Outline of Final Research Achievements |
Transcriptome analysis indicated that one gene encoding Schizont Infected Cell Agglutination variant (SICAvar) protein was transcribed in the binding P. knowlesi parasites significantly more than the non-binding P. knowlesi parasites. The cytoadhesion activity of the identified SICAvar protein to human umbilical vein endothelial cells (HUVECs) was confirmed using a transgenic parasite over-expressing this SICAvar protein.
Binding assay of a panel of recombinant SICAvar proteins with HUVECs revealed that the binding activity of a fragment possessing 2 CRDs was equivalent to the recombinant protein containing entire extracellular region, suggesting 2 CRDs was responsible for the binding to HUVECs.
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| Academic Significance and Societal Importance of the Research Achievements |
東南アジアに生息するマカク属サルを自然宿主とするサルマラリア原虫Plasmodium knowlesiはヒトにも自然感染することが知られており、ヒト感染における重篤化機序の解明が必要であるにも関わらず、P. knowlesi感染赤血球の接着機構に関する研究報告はほとんどなされていない。
本研究により、P. knowlesi感染赤血球のヒト血管内皮細胞への接着に関与すると考えられるSICAvar遺伝子を同定し、その組換え原虫や組換えタンパク質によりヒト血管内皮細胞への結合性を確認できたことは、
P. knowlesi 感染赤血球の接着機構及び血管の塞栓による重篤化機序の解明に繋がる。
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