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Studies on the Molecular Biology of Wild Type and Attenuated Strains of Japanese Encephalitis Virus.

Ni, Haolin. (1994) Studies on the Molecular Biology of Wild Type and Attenuated Strains of Japanese Encephalitis Virus. Doctoral thesis, University of Surrey (United Kingdom)..

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The aim of this project is to study the molecular biology of Japanese encephalitis (JE) virus. Comparison of the nucleotide and amino acid sequence of live attenuated JE vaccine virus SA14-2-8 with its virulent wild-type parent SA14 virus, and two other attenuated vaccine viruses derived from SA14 virus (SA14-14-2/PHK and SA14-14-2/PDK) revealed that only five amino acids in the parental SA14 virus have been substituted in all three attenuated vaccines. The two amino acids substituted in the E protein (E-138 and E-176) may attenuate the JE vaccine viruses by altering the virus-cell receptor interaction while the mutations in nonstructural protein 2B (NS2B-63) and NS3-105 are in functional domains of the virus-specified trypsin-like serine proteinase. Thus, attenuation of the vaccine viruses may, in part, be due to an altered viral proteinase activity which could affect the replication cycle of the virus. The genome of the highly mouse neuroinvasive wild-type strain P3 was also sequenced and compared to that of two other wild-type JE viruses that are poorly neuroinvasive in mice. The results suggested that the structural, NS2B and NS5 proteins and 3’ non-coding region may be involved in the increased neuroinvasiveness of P3 strain. Strain variation of wild-type JE virus was examined by comparing the 5’ terminal 2434 nucleotides. The amino acid homology of the envelope (E) protein gene of the viruses was 95. 8% or greater. Full genomic homologies of JE virus strains SA14, JaOArS982 and P3 were higher than 98% at both nucleotide and amino acid levels. Four variable E protein amino acids (E-51, E-209, E-244 and E-366) were identified. E-51, E-244 and E-366 are found in peptides with functional T-helper cell epitopes in two other flaviviruses. Therefore, these amino acids may be important in defining the imunotypes of JE virus.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Ni, Haolin.
Date : 1994
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1994.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 14:06
Last Modified : 06 May 2020 14:09

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