Studies on the effect of the virus isolation and passage for the original viral entry route

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460563
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SHIRATO Kazuya 国立感染症研究所, ウイルス第三部, 主任研究官 (40415477)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒトコロナウイルス / 継代 / カテプシンL / TMPRSS2

Outline of Final Research Achievements

Many enveloped viruses enter cells through endocytosis. Viral spike proteins drive the fusion of viral and endosomal membranes to facilitate insertion of the viral genome into the cytoplasm. Human coronavirus 229E (HCoV-229E) utilizes endosomal cathepsin L to activate the spike protein after receptor binding. Here, we found that clinical isolates of HCoV-229E preferentially utilize the cell surface protease TMPRSS2 rather than endosomal cathepsin L. The endosome is a main site of Toll-like receptor recognition, which then triggers an innate immune response; therefore, HCoV-229E presumably evolved to bypass the endosome by entering the cell via TMPRSS2. Thus, the virus uses a simple mechanism to evade the host innate immune system. Therefore, therapeutic agents for coronavirus-mediated diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), should target cell surface TMPRSS2 rather than endosomal cathepsin

Free Research Field

ウイルス学