| Project/Area Number |
18590453
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
OKAZAKI Katsunori Health Sciences University of Hokkaido, Dept of Pharmaceutical Sciences, Professor (90160663)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Emi Health Sciences University of Hokkaido, Dept of Pharmaceutical Sciences, Assistant Professor (80433423)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | influenza virus / hemaaelutinin / α-helix / synthetic peptide / pandemic / monoclonal antibod / MHC class II molecule / ペプチド / 抗体医薬 / モノクローナル抗本 / パラミクソウイルス / ヘルペスウイルス / 糖蛋白 / 膜融合 / 抗ウイルス作用 |
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| Research Abstract |
We found that each subtype (H1-H16) of influenza virus hemagglutinin (HA) contained the consensus sequence in a-helix region of HA2 subunit of the glycoprotein. Virus replication in MDCK cells was reduced by 10% when synthetic peptides with this sequence were added in the medium. Since the peptides seemed to interfere with proper folding of HA in the cells, the peptides were transfected into the cells using Chariot, which is capable of efficiently delivering peptide into cultured cells independently of the endosomal pathway. No inhibition was found by delivering the peptides before or after virus inoculation. These data may indicate that the endosomal pathway for delivering the peptides is much effective in the interference of the folding of HA, which is carried out in the intracellular vesicle system.
To prepare for the future pandemic of influenza, we attempted to produce monoclonal antibodies against H5 and H2 subtypes of HA. Seven amino acid residues common to each virus strain tested were found in the globular head of HA of both HA subtypes and introduced into the frame component bound to mouse I -A^b MHC class II molecule. The splenocytes from C57BL/6 mice immunized with the synthetic peptides containing the seven residues were used to prepare hybridoma cells. One cell line was found to produce neutralizing antibodies against A/Singapore/1/57 (H2N2) influenza virus. Although cross-reactivity with H5 virus of the antibodies is not yet studied, it is expected that the antibodies would provide therapeutic means for future pandemic of influenza.
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