Evasion of host-defense mechanism by autophagy regulatory gene encoded by cytomegalovirus.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08844
• 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: Gifu Pharmaceutical University
• Principal Investigator: Koshizuka Tetsuo 岐阜薬科大学, 薬学部, 教授 (20416267)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: サイトメガロウイルス / Nedd4 family / ユビキチン化 / 免疫回避

Outline of Final Research Achievements

To elucidate the mechanism by which viruses hijack the host cells, we tried to determine the functions of the cytomegalovirus (CMV) encoded gene products. The human CMV UL42 gene product regulates the activities of the host ubiquitin ligase Nedd4 family, which ubiquitinates proteins to change the fate of proteins. In the presence of UL42, some member of Nedd4 family proteins are degradated by the hyperubiquitination. In this regard, we identified that some member of Nedd4 family proteins were able to ubiquitinate a major viral glycoprotein gB and UL42 protected gB by the elimination of Nedd4 family proteins in infected cells. We are currently conducting detailed studies on the regulation of host cell surface proteins which affected by the UL42 function.

Free Research Field

ウイルス感染症

Academic Significance and Societal Importance of the Research Achievements

CMVは200を超える遺伝子を保持しており、これらを利用して宿主細胞をウイルス増殖に適した環境に作り変える。これによりウイルスは自身の増殖を可能とし、免疫応答を回避する。本研究で主な解析対象としたUL42は宿主ユビキチンリガーゼの活性を制御することで、ウイルス側分子の安定化や免疫関連分子機能を阻害といった多様な機能を担う可能性があることを明らかにした。本研究の成果は、ウイルスが宿主細胞を乗っ取り、免疫を回避し、発症に至る過程を理解するために重要であり、新規抗ウイルス化合物の標的となる可能性がある。