| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| 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.
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