Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice

Kate D. Ryman, Hong Xie, T. Neil Ledger, Gerald Campbell, Alan Barrett

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The live-attenuated yellow fever (YF) vaccine virus, strain 17D-204, has long been known to consist of a heterologous population of virions. Gould et al. (J. Gen. Virol. 70, 1889-1894 (1989)) previously demonstrated that variant viruses exhibiting a YF wild-type-specific envelope (E) protein epitope are present at low frequency in the vaccine pool and were able to isolate representative virus variants with and without this epitope, designated 17D(+wt) and 17D(-wt), respectively. These variants were employed here in an investigation of YF virus pathogenesis in the mouse model. Both the 17D-204 parent and the 17D(+wt) variant viruses were lethal for adult outbred mice by the intracerebral route of inoculation. However, the 17D(-wt) variant was significantly attenuated (18% mortality rate) and replicated to much lower titer in the brains of infected mice. A single amino acid substitution in the envelope (E) protein at E-240 (Ala → Val) was identified as responsible for the restricted replication of the 17D(-wt) variant in vivo. The 17D(+wt) variant has an additional second-site mutation, believed to encode a reversion to the neurovirulence phenotype of the 17D-204 parent virus. The amino acid substitution in the E protein at E-173 (Thr → Ile) of the 17D(+wt) variant which results in the appearance of the wild-type-specific epitope or nucleotide changes in the 5' and 3' noncoding regions of the virus are proposed as candidates.

Original languageEnglish (US)
Pages (from-to)376-380
Number of pages5
JournalVirology
Volume230
Issue number2
DOIs
StatePublished - Apr 14 1997

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Yellow fever virus
Viruses
Phenotype
Epitopes
Amino Acid Substitution
Yellow Fever Vaccine
Yellow Fever
Attenuated Vaccines
Proteins
Virion
Vaccines
Nucleotides
Mutation
Mortality
Brain
Population

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice. / Ryman, Kate D.; Xie, Hong; Ledger, T. Neil; Campbell, Gerald; Barrett, Alan.

In: Virology, Vol. 230, No. 2, 14.04.1997, p. 376-380.

Research output: Contribution to journalArticle

Ryman, Kate D. ; Xie, Hong ; Ledger, T. Neil ; Campbell, Gerald ; Barrett, Alan. / Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice. In: Virology. 1997 ; Vol. 230, No. 2. pp. 376-380.
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