| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Recent studies have revealed that the Gag or matrix proteins of many enveloped RNA viruses including retro-, rhabdo-, arena-, and filoviruses possess a so-called L-domain containing PPxY, PT/SAP, or YPxL, which are critical motifs for efficient budding. PPxY, PT/SAP, or YPxL motifs interact with cellular Nedd4-like ubiquitin ligases, Tsg101, or AIP1/ALIX, respectively. These host factors are involved in class E vacuolar protein-sorting (VPS) pathway, suggesting that the budding into the lumen of multivesicular bodies (MVBs) and viral budding at plasma membrane are topologically identical and share a common mechanism. In this study, to clarify the mechanism of budding of HTLV-1, M-PMV, Lassa and Influenza viruses and develop novel anti-viral strategies, we analyzed viral and cellular requirements for virus budding.
The followings are results from my studies.
1, Influenza virus requires viral M1, HA, NA and NP proteins for efficient VLP budding.
2, Lassa virus Z protein is sufficient for the release of virus like particle (VLP) and has PPPY as a functional L-domain.
3, Lassa virus uses cellular factors, Vps4A, Vps4B and Tsg101 in its budding, suggesting that Lassa virus budding uses MVB pathway functionally.
4, Although M-PMV and HTLV- 1 contains both PPxY and PT/SAP sequences, the PPxY sequence, but not the PSAP sequence, mainly functions as the viral L-domain in both viruses.
5, Tsg101 is involved in M-PMV budding in a PSAP-independent manner.
6, AIP 1/Alix and Vps4A/B are also involved in M-PMV budding, suggesting that M-PMV budding utilizes the cellular multivesicular body (MVB) sorting pathway.
7, PSAP motif plays an important role in earlier steps of M-PMV replication, but not in virus budding.
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