The elucidation of pathogenic mechanisms of vascular leakage and bone marrow suppression in dengue virus mouse model

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K14885
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KUROSU TAKESHI 国立感染症研究所, ウイルス第一部, 主任研究官 (70432432)
• Research Collaborator: OKUZAKI DAISUKE 大阪大学, 微生物病研究所, 助教 (00346131)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: デング出血熱 / マウスモデル / 出血熱 / サイトカインストーム / 血症漏出 / フラビウイルス / 重症感染症 / デングウイルス

Outline of Final Research Achievements

Dengue hemorrhagic fever is characterized by thrombocytopenia and plasma leakage. We tried to elucidate the mechanism of severity, and elucidated the mechanism of pathogenesis using several kinds of dengue virus infection mouse models. As a result, in the following process occurs during the process of severity 1) abnormal activation of the macrophage. 2) Excessive production of inflammatory cytokines such as TNF-α. 3) Battling protection factors and exacerbating factors in vascular endothelial cells. 4) Multiple organ failure due to cytokine storm occurred at the end of the disease state, and factors involved in each step were identified. In the bone marrow, it was concluded that the erythrocyte - megakaryocyte precursor cell disorder has occurred. Furthermore, for the application of mouse model, the protective ability test of the therapeutic antibody was carried out and its effectiveness was shown.

Free Research Field

ウイルス学