Phenotypic and genotypic characterization of the neurovirulence and neutroinvasiveness and a large-plaque attenuted Japanese encephalitis virus isolate

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Title:	Phenotypic and genotypic characterization of the neurovirulence and neutroinvasiveness and a large-plaque attenuted Japanese encephalitis virus isolate
Authors:	(Wu SC);林振文(Cheng-Wen Lin);(Lee SC);(Lian WC)
Contributors:	健康照護學院醫學檢驗生物技術學系;中國附醫檢驗醫學部
Keywords:	Japanese encephalitis virus;Neurovirulence;Neuroinvasiveness;Mouse brain passage
Date:	2003-05
Issue Date:	2009-08-26 16:00:37 (UTC+8)
Abstract:	The virulent phenotypes of Japanese encephalitis virus (JEV) can be divided into neuroinvasiveness (NI) and neurovirulence (NV). In this study, two JEV antigenic variants, CH2195LA (large-plaque, attenuated) and CH2195SA (small-plaque, non-attenuated), were passaged in suckling mice by intracerebral inoculation. Viruses at passage two and four were characterized in terms of NV and NI in weaning mice, as well as their in vitro growth characteristics in six cell lines. Following two brain-brain passages in mice, the attenuated variant CH2195LA was found to significantly restore the NV and NI by approximately 90% and 20–40%, respectively. The increased titers in THP-1 monocytic cells but not IMR-32 and Neuro-2A neuroblastoma cells were more correlated with the phenotypic changes of NI and NV in mice. Entire genomic sequencing was further performed to demonstrate that 14 nucleotides were altered in the attenuated variant CH2195LA following four brain-brain passages in mice, giving 12 amino acid changes, in prM-73, prM-80, E-161, E-170, E-276, NS2A-136, NS2A-215, NS3-346, NS4A-128, NS4B-196, NS4B-197, NS4B-198. This study indicated a cluster of amino acids which is involved in NV and NI of the JEV for mice and, perhaps, for humans. Elucidating the molecular basis of virulence of flaviviruses can provide valuable information for live-attenuated vaccine development.
Relation:	MICROBES AND INFECTION 5(6)475~480
Appears in Collections:	[Department of Medical Laboratory Science and Biotechnology ] Journal articles

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