Pathogenicity of multiple organ failure induced by seasonal and highly pathogenic avian influenza virus infection and its therapeutic options

2014 Fiscal Year Final Research Report

• Project/Area Number: 24249059
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: The University of Tokushima
• Principal Investigator: KIDO Hiroshi 徳島大学, 疾患酵素学研究センター, 特任教授 (50144978)
• Co-Investigator(Renkei-kenkyūsha): CHIDA Junji 徳島大学, 疾患酵素学研究センター, 助教 (10437651) ; MIZUNO Dai 徳島大学, 疾患酵素学研究センター, 助教 (70380061)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: インフルエンザ / 重症化機序 / 治療法 / バイオマーカー / 診断法 / 多臓器不全 / エネルギー代謝 / 血管透過性亢進

Outline of Final Research Achievements

Influenza A virus (IAV) causes significant morbidity and mortality. We have studied the viral pathogenicity and the host cellular factors involved in the pathogenicity of multiorgan failure (MOF). We proposed a new concept on the pathogenicity of MOF, the“influenza virus-cytokine-trypsin”cycle interconnected with the“metabolic disorders-cytokine". These cycles provide new treatment concepts for ATP crisis and MOF. One is diisopropylamine dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase 4 for glucose metabolism and the other is bezafibrate which up-regulates long-chain fatty acid metabolism. We also identified that IAV infection induces GSK-3β-mediated β-catenin degradation in the adherens junctional complexes and induces vascular hyperpermeability. Furthermore, we established SmartAmp system for detection of thermolabile carnitine palmitoyltransferase 2 SNPs as risk factors for influenza associated encephalopathy in the infected young children.

Free Research Field

病態医科学