Elucidation of spatiotemporal regulation of mumps virus RNA synthesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07584
• 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: National Institute of Infectious Diseases
• Principal Investigator: Katoh Hiroshi 国立感染症研究所, ウイルス第三部, 室長 (80711712)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ムンプスウイルス / RNA合成 / R2TP複合体 / 自然免疫

Outline of Final Research Achievements

The regulation of paramyxovirus RNA synthesis by host proteins is poorly understood. Here, we identified a novel regulation mechanism of paramyxovirus RNA synthesis by the Hsp90 co-chaperone R2TP complex. We showed that the R2TP complex interacted with the paramyxovirus polymerase L protein and that silencing of the R2TP complex led to uncontrolled upregulation of mumps virus (MuV) gene transcription but not genome replication. Regulation by the R2TP complex was critical for MuV replication and evasion of host innate immune responses. The R2TP complex also regulated measles virus (MeV) RNA synthesis, but its function was inhibitory and not beneficial to MeV, as MeV evaded host innate immune responses in the absence of the R2TP complex. The identification of the R2TP complex as a critical host factor sheds new light on the regulation of paramyxovirus RNA synthesis.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究では、パラミクソウイルスのRNA合成を制御する新たな宿主因子として、R2TP複合体を同定し、その機能を明らかにした。さらにR2TP複合体による厳密なウイルスRNA合成の制御が宿主免疫からの回避に必須であることも示された。パラミクソウイルス感染症の治療標的の一つであるウイルスRNA合成の理解は、抗パラミクソウイルス薬の開発に重要な知見となる。