STUDY ON THE NUEROVIRULENCE OF RECENT HUMAN INFLUENZA VIRUSES
| Project/Area Number |
10670289
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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 | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
NOBUSAWA Eri NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, ASSOCIATE PROFESSOR, 医学部, 助教授 (90183904)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Mituo FUKUOKA UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT, 医学部, 講師 (70299543)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | influenza virus / encephalitis / encephalopathy |
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| Research Abstract |
Etiology of the acute encephalitis/encephalopathy associated with influenza virus infection remained to be under investigation in Japan. Cleavage of the hemagglutinin by protease is a prerequisite for the pathogenicity and even for the neurovirulence of influenza A viruses. Novel influenza viruses which grew in MDCK cells in the absence of trypsin (NV virus) were isolated from patients with acute influenza encephalitis/encephalopathy. We have investigated the neurovirulence of the NV viruses in vivo and in vitro. Mice inoculated intracerebrally with WSN, a neurovirulent virus, adapted to mouse brain showed neurological symptoms and showed positive immunoreactivity to the anti-WSN antibody in meningeal regions. Mice inoculated with NV viruses, however, did not show any neurological symptoms and immunoreactivity to the anti-H3N2 virus antibody. Human neuroblastoma and glioblastoma cells were also infected with NV viruses in the presence and absence of trypsin. NV viruses could not grow in the both kind of cells in the absence of trypsin,, while WSN grew in the both cells without trypsin. These results showed that the trypsin independent growth ability of NV viruses could not necessarily explain their neurovirulence. Since the increase of interleukin-6 (IL-6) in the plasma and CSF (cerebro spinal fluid) of patients was reported, we have investigated the ability of NV viruses to induce IL-6 in the human microvascular endothelial cells, but NV viruses could not induce IL-6 in these cell. We also tried to detect influenza viruses or genome in the CSF by using a system which can detect viruses and genome in CSF if viruses exist at more than 1 PFU. All the CSF of 10 patients were examined, but neither viruses nor genome were detected. These results suggested that direct invasion of the influenza viruses into the central nervous system was uncommon event.
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Report
(3 results)
Research Products
(15 results)
