2012 Fiscal Year Final Research Report
Pathogenesis of spongiform encephalopathy induced by viral infection
| Project/Area Number |
22590368
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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 |
Experimental pathology
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| Research Institution | Soka University |
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Principal Investigator |
WATANABE Rihito 創価大学, 工学部生命情報工学科, 教授 (30129746)
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| Co-Investigator(Renkei-kenkyūsha) |
TAGUCHI Fumihiro 日本獣医生命科学大学, 獣医学部, 教授 (30107429)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 単球 / 海綿状脳症 / 初期病変 |
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| Research Abstract |
Mouse hepatitis virus (MHV) is a member of the coronavirus family. Spike (S) protein, composed of virion projections, is responsible for binding to a receptor and also for the cell entry mechanism of MHV. Soluble receptor-resistant mutant 7 (srr7) isolated from the highly neuropathogenic JHM strain of MHV, cl-2, shows slightly reduced virulence compared to its maternal virus, inducing spongiotic degeneration at 48 hours post-inoculation (pi) with viral antigens-expression in the periventricular areas.During the course of infection with srr7, small spongiotic lesions appear at 2 days pi,and these spread out to form spongiform encephalopathy by 8 to 10 days pi. In thisstudy, we noted that the neurovirulence of srr7 increases with a shorter incubationperiod, and, in some cases, exhibits infectivity of neurons, similar to the observation incl-2 infection. Through the re-cloning of srr7, we obtained several mutants with singleor double substitutions of amino acids in the S protein rei on. All of these mutantviruses exhibited major MHV receptor (MHVR)-independent infectivity due to themutation of the S-coding region, which was examined by in vitro expression of thegenes. Each mutant virus showed different pattern of invasion into the brainparenchyma, provably due to the difference in the affinity to extracellular matrixemerged after the infection in the brain, which provides a new paradigm to elucidatethe mechanisms of spongiotic degeneration in the brain.
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