Mutation in a 17D-204 vaccine substrain-specific envelope protein epitope alters the pathogenesis of yellow fever virus in mice

Kate D. Ryman, T. Neil Ledger, Gerald Campbell, Stanley Watowich, Alan Barrett

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The heterogeneous nature of the yellow fever (YF) 17D-204 vaccine virus population was exploited in this study to isolate virus variants able to escape neutralization by the 17D-204 vaccine-specific MAb 864. The conformational change on the virus surface that resulted in the loss of the MAb 864-defined epitope was effected in each variant by a single amino acid mutation in the envelope (E) protein at either position E-305 or E-325. Interestingly, both positions were mutated during attenuation of the 17D-204 vaccine substrain from the wildtype Asibi strain. The mutations in several of the variants represented reversion to the wildtype Asibi virus sequence consistent with loss of a 17D-204 substrain-specific epitope. The majority of the variant viruses were shown to have altered mouse neurovirulence phenotypes, ranging from complete avirulence through to increased virulence. The avirulent variants are the first flavivirus MAb-neutralization-resistant variants to be attenuated for neurovirulence in the adult mouse model. Overall, the results indicate that the E protein epitope recognized by MAb 864 defines a functionally important region that encodes major molecular determinants of YF virus pathogenesis in vivo.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalVirology
Volume244
Issue number1
DOIs
StatePublished - Apr 25 1998

Fingerprint

Yellow fever virus
Epitopes
Vaccines
Viruses
Mutation
Proteins
Yellow Fever
Flavivirus
Virulence
Phenotype
Amino Acids
Population

Keywords

  • 17D-204 substrain-specific epitope
  • Envelope protein
  • Yellow fever virus

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Mutation in a 17D-204 vaccine substrain-specific envelope protein epitope alters the pathogenesis of yellow fever virus in mice. / Ryman, Kate D.; Ledger, T. Neil; Campbell, Gerald; Watowich, Stanley; Barrett, Alan.

In: Virology, Vol. 244, No. 1, 25.04.1998, p. 59-65.

Research output: Contribution to journalArticle

@article{27c9f513e7b247509e65dbaef139d9ad,
title = "Mutation in a 17D-204 vaccine substrain-specific envelope protein epitope alters the pathogenesis of yellow fever virus in mice",
abstract = "The heterogeneous nature of the yellow fever (YF) 17D-204 vaccine virus population was exploited in this study to isolate virus variants able to escape neutralization by the 17D-204 vaccine-specific MAb 864. The conformational change on the virus surface that resulted in the loss of the MAb 864-defined epitope was effected in each variant by a single amino acid mutation in the envelope (E) protein at either position E-305 or E-325. Interestingly, both positions were mutated during attenuation of the 17D-204 vaccine substrain from the wildtype Asibi strain. The mutations in several of the variants represented reversion to the wildtype Asibi virus sequence consistent with loss of a 17D-204 substrain-specific epitope. The majority of the variant viruses were shown to have altered mouse neurovirulence phenotypes, ranging from complete avirulence through to increased virulence. The avirulent variants are the first flavivirus MAb-neutralization-resistant variants to be attenuated for neurovirulence in the adult mouse model. Overall, the results indicate that the E protein epitope recognized by MAb 864 defines a functionally important region that encodes major molecular determinants of YF virus pathogenesis in vivo.",
keywords = "17D-204 substrain-specific epitope, Envelope protein, Yellow fever virus",
author = "Ryman, {Kate D.} and Ledger, {T. Neil} and Gerald Campbell and Stanley Watowich and Alan Barrett",
year = "1998",
month = "4",
day = "25",
doi = "10.1006/viro.1998.9057",
language = "English (US)",
volume = "244",
pages = "59--65",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Mutation in a 17D-204 vaccine substrain-specific envelope protein epitope alters the pathogenesis of yellow fever virus in mice

AU - Ryman, Kate D.

AU - Ledger, T. Neil

AU - Campbell, Gerald

AU - Watowich, Stanley

AU - Barrett, Alan

PY - 1998/4/25

Y1 - 1998/4/25

N2 - The heterogeneous nature of the yellow fever (YF) 17D-204 vaccine virus population was exploited in this study to isolate virus variants able to escape neutralization by the 17D-204 vaccine-specific MAb 864. The conformational change on the virus surface that resulted in the loss of the MAb 864-defined epitope was effected in each variant by a single amino acid mutation in the envelope (E) protein at either position E-305 or E-325. Interestingly, both positions were mutated during attenuation of the 17D-204 vaccine substrain from the wildtype Asibi strain. The mutations in several of the variants represented reversion to the wildtype Asibi virus sequence consistent with loss of a 17D-204 substrain-specific epitope. The majority of the variant viruses were shown to have altered mouse neurovirulence phenotypes, ranging from complete avirulence through to increased virulence. The avirulent variants are the first flavivirus MAb-neutralization-resistant variants to be attenuated for neurovirulence in the adult mouse model. Overall, the results indicate that the E protein epitope recognized by MAb 864 defines a functionally important region that encodes major molecular determinants of YF virus pathogenesis in vivo.

AB - The heterogeneous nature of the yellow fever (YF) 17D-204 vaccine virus population was exploited in this study to isolate virus variants able to escape neutralization by the 17D-204 vaccine-specific MAb 864. The conformational change on the virus surface that resulted in the loss of the MAb 864-defined epitope was effected in each variant by a single amino acid mutation in the envelope (E) protein at either position E-305 or E-325. Interestingly, both positions were mutated during attenuation of the 17D-204 vaccine substrain from the wildtype Asibi strain. The mutations in several of the variants represented reversion to the wildtype Asibi virus sequence consistent with loss of a 17D-204 substrain-specific epitope. The majority of the variant viruses were shown to have altered mouse neurovirulence phenotypes, ranging from complete avirulence through to increased virulence. The avirulent variants are the first flavivirus MAb-neutralization-resistant variants to be attenuated for neurovirulence in the adult mouse model. Overall, the results indicate that the E protein epitope recognized by MAb 864 defines a functionally important region that encodes major molecular determinants of YF virus pathogenesis in vivo.

KW - 17D-204 substrain-specific epitope

KW - Envelope protein

KW - Yellow fever virus

UR - http://www.scopus.com/inward/record.url?scp=0032565395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032565395&partnerID=8YFLogxK

U2 - 10.1006/viro.1998.9057

DO - 10.1006/viro.1998.9057

M3 - Article

C2 - 9581778

AN - SCOPUS:0032565395

VL - 244

SP - 59

EP - 65

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -