Study on the molecular mechanism of neuropathogenicity of a subacute sclerosing panencephalitis (SSPE) virus

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08941
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: ITOH Masae 長浜バイオ大学, バイオサイエンス学部, 教授 (10201328)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: SSPEウイルス / 神経病原性 / 持続感染 / 麻疹ウイルス

Outline of Final Research Achievements

Characterization of the all mutations detected in the genome of the Kobe-1 strain of subacute sclerosing panencephalitis (SSPE) virus was performed with the aim to unravel the whole aspect of the molecular mechanism through which a parental measles virus evolved into an SSPE virus in the brain of a patient taking several years. In the P, F, H and L proteins, amino acid mutations that suppress the function of each viral protein were identified; recombinant viruses bearing those mutations decreased their propagation in neuronal cells. At the stage of disease onset, the Kobe-1 strain should have increased its cell-to-cell fusion ability obtaining mutations in the F and M proteins, which accelerated viral spread in the brain. Mutations that cause the opposite effect on the virus to reduce its growth might have been indispensable for the measles virus to establish persistent infection just after invasion into the brain before acquiring enhanced cell-to-cell fusion ability.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

SSPEは、麻疹治癒後も麻疹ウイルスが脳内に持続感染し、5から10年を経て稀に発症する致死的疾患である。発症前の変異途上のウイルスを得ることはできず、本研究において、発症後に分離されたウイルスのゲノム上の全変異を解析することにより、初めて持続感染の分子機構を推察するに至った。今後、他のSSPEウイルス株において同様の解析を積み重ね、病原性発現機構の全体像が明らかとなれば、未だ科学的根拠が不明なワクチン株がSSPEを発症しない理由の解明へと展開でき、同時に、治療法や治療薬開発の可能性につながるものと期待される。