Host Factors involved in the formation of Flavivirus replication organelle

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Hirosaki University
• Principal Investigator: Morita Eiji 弘前大学, 農学生命科学部, 准教授 (70344653)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: フラビウイルス / ESCRT / 宿主因子

Outline of Final Research Achievements

Flavivirus, including dengue virus and Japanese encephalitis virus (JEV), infection induces endoplasmic reticulum (ER) membrane rearrangements to crate a compartment for replication of the viral genome and assembly of viral particles. By extensive mass spectrometry analysis, we identified ESCRT (endosomal sorting complex required for transport) factors that are recruited to sites of virus replication. Systematic siRNA analysis revealed that release of JEV was dramatically decreased by single depletion of TSG101 or co-depletion of specific combinations of CHMP family proteins. By contrast, release was unaffected by depletion of some core ESCRTs, including VPS4. Thus, a unique subset of ESCRT contributes to ER membrane biogenesis during flavivirus infection. This unique ESCRT requirement implies the existence of ER-specific features for ESCRT-mediated membrane rearrangement, and our study provides the first demonstration of the mechanistic features of ER ESCRTs.

Free Research Field

ウイルス学