The molecular mechanism of HCV-induced protein degradation via chaperone mediated autophagy

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16671
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Kobe University
• Principal Investigator: Matsui Chieko 神戸大学, 医学研究科, 助教 (70778414)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: C型肝炎ウイルス / NS5A蛋白質 / シャペロン介在性オートファジー / HSC70 / LAMP-2A / 選択的蛋白質分解 / CMA標的配列

Outline of Final Research Achievements

Chaperone mediated autophagy (CMA) carries a substrate protein into the lysosomal lumen using HSC70 and LAMP-2A. Substrate proteins of CMA contain a CMA-targeting motif, which is selectively recognized by HSC70. CMA promotes the degradation of a specific substrate protein that enters into the lysosome through LAMP-2A. We previously reported that HCV NS5A interacts with HSC70 and recruits HSC70 to substrate protein, thereby promoting the lysosomal degradation of substrate protein via CMA. More than 130 host proteins have been identified as NS5A-interacting proteins. In this study, we examined the potential CMA-targeting motif in NS5A interacting proteins. We found novel host proteins that are degraded by lysosomes via the CMA-dependent pathway.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

シャペロン介在性オートファジー(CMA)は、分解される宿主蛋白質が5アミノ酸からなるCMA標的配列を有していることが条件となる選択的分解機構である。
本研究では、HCV NS5A結合因子の中からシャペロン介在性オートファジーで分解誘導される新規宿主因子を同定した。さらなるHCV感染とCMAの解析により、HCV感染による新しい病原性発現機構の解明と治療法開発の端緒となることが期待できる。