Identification of novel proteases involved in the regulation of highly pathogenic avian influenza (HPAI) viruses infection

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591481
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Sagami Women's University (2013-2014); The University of Tokushima (2012)
• Principal Investigator: YUUSHI Okumura 相模女子大学, 公私立大学の部局等, 教授 (70294725)
• Co-Investigator(Kenkyū-buntansha): NIKAWA Takeshi 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授 (20263824) ; HIRASAKA Katsuya 長崎大学, 水産学部, 助教 (70432747)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 高病原性鳥インフルエンザウイルス / ウイルス活性化酵素 / 膜結合型プロテアーゼ / プロテアーゼ阻害剤

Outline of Final Research Achievements

Cleavage of viral envelope glycoprotein, hemagglutinin (HA), by host cellular proteases is essential step for influenza virus to enter into the target cells. We identified that ubiquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, were candidates of HA-processing proteases of diverse highly pathogenic avian influenza (HPAI) viruses. To confirm the involvement of these proteases in HPAI virus infection, highly virulent virus (A/Crow/Kyoto/53/2004 (H5N1)) was infected into MSPL/TMPRSS13 stably expressed cells and MSPL/TMPRSS13-deficient mice (MSPL/TMPRSS13-/-). As a result, we concluded that these proteases productions might be responsible for HPAI virus multicycle replication and spreading. We next succeeded to reveal the crystal structure of MSPL/TMPRSS13. Based on their structure, we generated specific inhibitors for MSPL/TMPRSS13. In vivo infectious experiments using their specific inhibitors are currently being investigated.

Free Research Field

生化学・分子生物学