1999 Fiscal Year Final Research Report Summary
Molecular Mechanism of Host Damage by Influenza Virus Infection and its Application
| Project/Area Number |
09670326
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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 | Institute for Developmental Research |
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Principal Investigator |
TAKIZAWA Takenori Institute for Developmental Research, Department of Biochemistry, Section Head, 生化学部, 室長 (40192158)
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| Project Period (FY) |
1997 – 1999
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| Keywords | influenza virus / apoptosis / caspase / Fas / PKR |
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| Research Abstract |
We found that the Influenza virus infection induces apoptosis of host cells which was accompanied with the augmented expression of Fas and its ligand, as well as the activation of apoptotic cysteine proteases, caspases. Double stranded-RNA activated protein kinase (PKR) was thought to play a crucial role in Fas expression and apoptotic signal transduction upon viral infection or Fas stimulation. To elucidate the mechanism of the virus-induced apoptosis, we examined the effect of inhibitors of caspases. We found that caspase-3 inhibitor (DEVD) and virus-encoded caspase inhibitors of caspases. We found that caspase-3 inhibitor (DEVD) and virus-encoded caspase inhibitor of crmA and vFLIP inhibited the virus-induced apoptosis. DEVD, however, did not inhibit viral replication, suggesting that caspase activation is downstream of viral growth. Recombinant plasmids encoding Influenza virus NS1 fused to enhanced green fluorescence protein (EGFP) in its C-terminus were constructed. These plasmids also contained the peptide inhibitors of caspases between NS1 and EGFP. Transfection of the plasmid containing DQMD or DEVD sequence into 293 cells suppressed the apoptosis by influenza virus infection, indicating that recombinant virus encoding NS1 protein with caspase inhibitor attenuates host damage. NS1-EGFP fusion proteins revealed to inhibit PKR activity, suggesting that the fusion proteins are functional. Construction of recombinant viruses with NS1-caspase inhibitors and their effect on host damage in vivo will be investigated in near future.
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Research Products
(16 results)
