Identification of influenza virus mutations responsible for the efficient replication in humans and analysis of the effect of the mutations on pathogenicity in animal models
| Project/Area Number |
22790426
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
YAMADA Shinya 東京大学, 医科学研究所, 特任助教 (90466839)
|
|---|
| Project Period (FY) |
2010 – 2011
|
| 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)
|
|---|
| Keywords | インフルエンザ / 伝播 / 変異 |
|---|
| 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.
|
Report
(3 results)
Research Products
(21 results)
-
[Journal Article] Adaptation of a duck influenza A virus in quail.2012
Author(s)
Yamada S, Shinya K, Takada A, Ito T, Suzuki T, Suzuki Y, Le QM, Ebina M, Kasai N, Kida H, Horimoto T, Rivailler P, Chen LM, Donis RO, Kawaoka Y.
-
Journal Title
J Virol
Volume: 86(3)
Pages: 1411-20
URL
Related Report
Peer Reviewed
-
-
[Journal Article] Avian-type receptor-binding ability can increase influenza virus pathogenicity in macaques2011
Author(s)
Watanabe T, Shinya K, Watanabe S, Imai M, Hatta M, Li C, Wolter BF, Neumann G, Hanson A, Ozawa M, Yamada S, Imai H, et al
-
Journal Title
URL
Related Report
Peer Reviewed
-
[Journal Article] Replication-incompetent influenza A viruses that stably express a foreign gene.2011
Author(s)
Ozawa M, Victor ST, Taft AS, Yamada S, Li C, Hatta M, Das SC, Takashita E, Kakugawa S, Maher EA, Neumann G, Kawaoka Y.
-
Journal Title
URL
Related Report
Peer Reviewed
-
-
-
-
-
-
[Journal Article] The HA and NS genes of human H5N1 influenza A virus contribute to high virulence in ferrets2010
Author(s)
Imai H, Shinya K, Takano R, Kiso M, Muramoto Y, Sakabe S, Murakami S, Ito M, Yamada S, Le MT, Nidom CA, et al.
-
Journal Title
URL
Related Report
Peer Reviewed
-
-
-
-
-
[Presentation]2011
Author(s)
山田晋弥
Organizer
第8回日中連携研究室ワークショップ
Place of Presentation
北京(中華人民共和国)
Related Report
-
-
-
-
-
-
