Identification of compounds that selectively inhibit rabies virus replication

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14859
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ogawa Kenji 国立研究開発法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (50251418)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 人獣共通感染症

Outline of Final Research Achievements

Rabies virus phosphoprotein (P protein) play an important role in the virus replication and suppression of host immunity. We focused on the P protein as a drug target, and established assay for measuring (1) P protein dimerization, and the interaction between the P protein and (2) rabies virus nucleoprotein and (3) host dynein L chain based on the split-luciferase complementation assays. The assays can be adapted to a high-throughput format to identify novel anti-rabies virus compounds. We next examined the relationship between the dimerization and immunosuppressive activity of P protein. The split-luciferase assay and Western blotting revealed that a mutant P protein in which Tyr-128 was substituted with Ala (Y128A) was defective in dimerization. However, the Y128A mutant P protein has the immunosuppressive activity comparable to the wild-type P protein. Thus, different functional domains of the P protein may be responsible for the dimerization and immunosuppressive activity.

Free Research Field

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