Mutation in NS5 protein attenuates mouse neurovirulence of yellow fever 17D vaccine virus

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

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The 17D-204 vaccine manufactured in South Africa (17D-204-SA) and a large plaque variant (17D-LP) derived from it were highly virulent in adult mice. The LD50 of 17D-LP virus was 0.2 p.f.u. for mice following intracerebral inoculation. In comparison, a medium plaque variant derived from 17D-LP, termed 17D-MP virus, was found to be attenuated in adult mice following the same route of inoculation (> 104 p.f.u./LD50). Replication of 17D-MP virus was decreased in infected mouse brains compared to 17D-LP virus. Also, 17D-MP virus was slightly temperature sensitive at 39.5 °C. Compared to its parent viruses, 17D-204-SA and 17D-LP, 17D-MP virus had one unique mutation at nt 8045 in the genome which resulted in a single amino acid substitution (Pro→Ser) at residue 137 of the NS5 protein and appeared to be the mutation responsible for the attenuation of 17D-MP virus. This is the first time that altered virulence of a flavivirus caused by mutation in a non-structural protein gene, other than NS1, has been reported.

Original languageEnglish (US)
Pages (from-to)1895-1899
Number of pages5
JournalJournal of General Virology
Volume79
Issue number8
DOIs
StatePublished - Aug 1998

ASJC Scopus subject areas

  • Virology

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