Structural basis of innate immune evasion by Paramyxovirus C protein involving the binding to the novel counterpart

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Oda Kosuke 広島大学, 医系科学研究科(医), 助教 (60571255)
• Co-Investigator(Kenkyū-buntansha): 小田 隆 立教大学, 理学部, 助教 (00573164)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: センダイウイルス / C蛋白質 / 新規標的因子 / 自然免疫 / サイトカイン

Outline of Final Research Achievements

Paramyxovirus C proteins are extremely important for viral pathogenesis and exhibit a variety of functions when bound to target proteins, but not all of their functions can be fully explained by binding to existing target proteins alone. Recently, host protein X was identified as the novel counterpart of Sendai virus C protein. In this study, we found that the C-terminal region of C protein (Y3) and the N-terminal domain of X (XND) are the smallest regions sufficient for binding to each other. Affinity analysis revealed that Y3 binds to XND with 10-fold weaker affinity than the existing target proteins. Furthermore, viral infection experiments revealed that binding to a novel target protein X is important for the sensitivity of SeV to IFN-α.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

ウイルス蛋白質と宿主蛋白質間の一過性で弱い相互作用がウイルス病原性にどれほど関与するかは未だ不明な点が多い。本研究では, 弱い相互作用で結合する新規標的宿主蛋白質を同定し, この標的蛋白質と結合しないウイルス蛋白質をもつ組換えSeVを作出することで, ウイルス生活環における弱い相互作用の重要性を明らかにした。本成果は, パラミクソウイルスC蛋白質のインタラクトームに関する理解を深めるとともに, 感染症に対する治療・予防戦略の開発に資する。