Analysis of respiratory virus activation mechanism by bacterial proteases
| Project/Area Number |
15H04596
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Veterinary medical science
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
SAKAI KOUJI 国立感染症研究所, ウイルス第三部, 主任研究官 (70515535)
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| Co-Investigator(Kenkyū-buntansha) |
小川 道永 国立感染症研究所, 細菌第一部, 室長 (80361624)
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| Research Collaborator |
NAKAJIMA Katsuhiro
KITAZAWA Minori
Nathanan Sangsriratnakul
KOMURA Miyuki
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Keywords | 細菌性プロテアーゼ / インフルエンザAウイルス / 膜蛋白質 / 開裂 / 重症化肺炎 / 呼吸器ウイルス / 膜タンパク質 / インフルエンザウイルス / ウイルス / 細菌 / プロテアーゼ / 混合感染 |
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| Outline of Final Research Achievements |
The host protease TMPRSS2 plays an essential role in HA proteolytic activation of the influenza A virus (IAV) for the pathogenic expression of primary viral pneumonia. Secondary infectious pneumonia involving bacterial infection, accounts for the majority of IAV deaths, but the detailed mechanism is unknown. We preformed to verify using mouse model. However promotion of HA cleavage of IAV by bacterial protease was not observed. On the other hand, after passages in TMPRSS2 knockout mice, an H3N2 and H7N1 subtype IAVs began to undergo cleavage activation of HA, showing high virulence in the mice due to the loss of an oligosaccharide in the HA stalk region. Thus, these TMPRSS2 knockout mice adapted IAVs acquired cleavability by an alternative HA activation proteases.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus.2016
Author(s)
Sakai K, Ami Y, Nakajima N, Nakajima K, Kitazawa M, Anraku M, Takayama I, Sangsriratanakul N, Komura M, Sato Y, Asanuma H, Takashita E, Komase K, Takehara K, Tashiro M, Hasegawa H, Odagiri T, Takeda M.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 29430-29430
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Mutant H3N2 Influenza Virus Uses an Alternative Activation Mechanism in TMPRSS2 Knockout Mice by Loss of an Oligosaccharide in the Hemagglutinin Stalk Region2015
Author(s)
Sakai K, Sekizuka T, Ami Y, Nakajima N, Kitazawa M, Sato Y, Nakajima K, Anraku M, Kubota T, Komase K, Takehara K, Hasegawa H, Odagiri T, Tashiro M, Kuroda M, Takeda M
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Journal Title
J Virol
Volume: 89
Issue: 9
Pages: 5154-5158
DOI
Related Report
Peer Reviewed / Open Access
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