Determination of miRNA biomarkers in the pathogenesis of severe dengue

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08954
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: The University of Tokyo (2021-2022); Nagasaki University (2019-2020)
• Principal Investigator: Moi Meng Ling 東京大学, 大学院医学系研究科(医学部), 教授 (40597499)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: dengue / miRNA

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.

Free Research Field

Virology

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.