| Project/Area Number |
22790426
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMADA Shinya 東京大学, 医科学研究所, 特任助教 (90466839)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | インフルエンザ / 伝播 / 変異 |
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| Research Abstract |
The efficient transmission of H5N1 viruses among humans has never occurred, suggesting that the further adaptation to humans is required. At the moment, little is known about mutations responsible for the efficient transmission of H5N1 viruses in humans. Two amino acids(lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals. Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice.
We also report that H5N1viruses isolated from human in Vietnam in 2004 became to grow higher through the passages in normal human bronchus epithelial(NHBE) cells by acquiring several mutations. Mainly mutations in hemagglutinin(HA) genes were responsible for their high growth. However, no transmission of the mutant viruses via respiratory droplets in ferret model was observed.
In this study, we identified some new molecular markers responsible for the efficient replication of influenza viruses in human cells.
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