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Title: Studies on zoonotic Japanese encephalitis virus Muar strain
Author: Mohammed, Manal Ahmed Farid
ISNI:       0000 0004 2737 0335
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2011
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Japanese encephalitis virus (JEV) is the most important cause of epidemic encephalitis worldwide but its origin is unknown. Epidemics of encephalitis suggestive of Japanese encephalitis (JE) were described in Japan from the 1870s onwards. Four genotypes of JEV have been characterised and representatives of each genotype have been fully sequenced. Based on limited information, a single isolate from Malaysia, the Muar strain, is thought to represent a putative fifth genotype. I have determined the complete nucleotide and amino acid sequence of the Muar strain and compared it with other fully sequenced JEV genomes. Muar was the least similar, with nucleotide divergence ranging from 20.2 to 21.2% and amino acid divergence ranging from 8.5 to 9.9%. Phylogenetic analysis of the Muar strain revealed that it does represent a distinct fifth genotype of JEV. I elucidated the Muar signature amino acids in the envelope (E) protein, including E327 Glutamine on the exposed lateral surface of the putative receptor binding domain of the E protein, which distinguishes the Muar strain from the other four genotypes. Evolutionary analysis of full-length JEV genomes revealed that the mean (range) evolutionary rate is 4.35 x 10-4 (3.4906 X 10-4 to 5.303 x 10-4) nucleotides substitutions per site per year and suggests JEV originated from its ancestral virus in the mid 1500s. It is postulated to have originated in the Indonesia-Malaysia region and evolved there into different genotypes, which then spread across Asia. No strong evidence for positive selection was found between JEV strains of the five genotypes and the E gene has generally been subjected to strong purifying selection. The ability of intravenous immunoglobulins (IVIGs) which sometimes are used as supportive treatment for JEV infection to protect against strains of JEV representing the five major genotypes was assessed. Neutralization assays showed IVIGs appear cross-reactive across the five JEV genotypes with effective but lower titers for the Muar strain as well as representatives from genotype IV. Whether there are other strains from genotype V, and what happened to them remains unknown.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral