Analysis of molecular mechanisms of CCHFV cell entry and the pathogenicity

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Nagasaki University
• Principal Investigator: Sakurai Yasuteru 長崎大学, 熱帯医学研究所, 助教 (00818338)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: クリミア・コンゴ出血熱ウイルス / 細胞侵入過程 / 病原性発現機序 / 膜融合 / 侵入阻害剤

Outline of Final Research Achievements

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus, which causes a severe infectious disease in human. The detailed molecular mechanisms of viral replication and pathogenicity as well as the difference between virus strains are still largely unknown.
In this study, we successfully produced pseudotyped virus bearing glycoproteins of multiple CCHFV strains and developed a quantitative assay for membrane fusion. These experimental tools can be useful for detailed and comparative analyses of CCHFV cell entry steps.
Moreover, using the newly-developed assays, pan-nairovirus fusion inhibitors were identified among FDA-approved drugs. Different sensitivities to neutralizing antibodies and external stimulus between viruses were also demonstrated. We expect that these results will contribute to development of antiviral therapy and disinfection method for CCHFV.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

野生型CCHFVはバイオセーフティーレベル4（BSL4）施設にて扱う必要があり、限られた研究者が限られた手法でしか研究出来ない。本研究で開発したシュードタイプウイルスや膜融合アッセイを用いることで、BSL-2実験室において細胞侵入過程の多面的な解析や、ウイルス株間での相違についての詳細な解析が可能となる。更に、本研究により中和抗体や外的刺激に対する特徴的な感受性が明らかになったことで、表面糖タンパク質を標的とした治療法やウイルス不活化方法の開発がより一層進むことも期待される。