| Project/Area Number |
19K08954
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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 54030:Infectious disease medicine-related
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| Research Institution | The University of Tokyo (2021-2022)
Nagasaki University (2019-2020) |
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Principal Investigator |
Moi Meng Ling 東京大学, 大学院医学系研究科(医学部), 教授 (40597499)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | dengue / miRNA / デング熱 |
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| Outline of Research at the Start |
In this study, we aim to define the miRNA dynamics in blood and body fluids using a novel approach of longitudinal miRNA transcriptional profiles to identify of host determinants and mechanisms that are responsible for modulating the balance between severe and non-severe Dengue.
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| Outline of Final Research Achievements |
In dengue, humoral and cellular immunity may play a dual role in disease pathogenesis and protection. We first analyzed 45 cytokines and other factors in serum samples from the acute phase of DENV infection from 167 patients.ignificant correlations were identified between disease severity and CCL5, SCF, PDGF-BB, IL-10, and TNF-α levels; between NS1 Ag and SCF, CCL5, IFN-α, IL-1α, and IL-22 levels; between thrombocytopenia and IL-2, TNF-α, VEGF-D, and IL-6 levels; and between primary or secondary infection and IL-2, IL-6, IL-31, IL-12p70, and MIP-1β levels. A total of 3 candidates identified from the mRNA profiles of dengue patients was synthesized. One candidate, miRNA hsa-let-7c-5p was selected for the following assays due to higher potency during infection. Virus growth was examined by using real-time PCR and plaque assay. We found that miRNA hsa-let-7c-5p inhibited dengue virus replication and is potentially associated with host response generated during DENV infection.
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| Academic Significance and Societal Importance of the Research Achievements |
miRNA hsa-let-7c-5p inhibited DENV replication and is potentially associated with host response generated during viral infection. These circulating factors may represent leading signatures in acute DENV infections, that are associated with clinical severity.
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