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Studies On The Structural Protein Genes of Attenuated Strains of Yellow Fever Virus.

Jennings, Alan David. (1993) Studies On The Structural Protein Genes of Attenuated Strains of Yellow Fever Virus. Doctoral thesis, University of Surrey (United Kingdom)..

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The aim of this study was to determine the nucleotide and deduced amino acid sequences of the structural protein genes of strains of yellow fever (YF) virus of defined phenotype. Specifically, two wild-type/vaccine pairs were examined, namely passage of wild-type strain Asibi virus through chick tissue to develop the 17D live vaccine strain (studied as the 17DD substrain), and the French viscerotropic virus (FVV) through mouse brain to develop the French neurotropic vaccine (FNV) strain. The atypical African wild-type YF virus, Y5, was also analyzed. In addition, the sequence of the envelope (E) protein genes of a neurovirulent revertant YF vaccine virus, and the vaccine batch from which it originated were also determined. In total, approximately 15 kilobases of nucleotide sequence data was generated in duplicate. Despite different routes of attenuation, the two vaccine strains were found to share an amino acid substitution in the membrane protein (35), and also to exhibit a cluster of substitutions in the E protein. The neurovirulent revertant vaccine virus was shown to differ from the parent vaccine virus at just two amino acid positions in the E protein (155 and 303), suggesting that one or both may be important in the appearance of the neurovirulent phenotype in YF virus. Atypical wild-type strain Y5 proved to differ by nearly 8% at the nucleotide level, but by less than 2% at the amino acid level from other African wild-type viruses. Three amino acid positions (325, 407 and 416) were identified which may be important in the appearance of an E protein epitope associated with attenuation of YF virus. Overall, the results obtained increase our knowledge of YF virus at the molecular level and indicate particular amino acids are involved in attenuation of virulence. Future work could examine some of the hypotheses presented, with the hope of identifying amino acids within the structural proteins of YF virus which may be critical in attenuation, neurovirulence, and antigenic markers seen in YF virus.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Jennings, Alan David.
Date : 1993
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1993.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 11:56
Last Modified : 06 May 2020 12:02

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