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Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses
Published on: December 29, 2015
Attenuated West Nile viruses bearing 3'SL and envelope gene substitution mutations
Li Yu1, J Robert Putnak, Alexander G Pletnev
1Laboratory of Vector-borne Virus Diseases, Division of Viral Products, FDA, Bethesda, MD 20892, USA. Li.Yu@fda.hhs.gov
Abstract:
Four viable West Nile (WN) 3'SL-mutant viruses were evaluated for neuroinvasiveness and neurovirulence in mice. All mutants were highly attenuated for neuroinvasiveness. However, only one of these four (WNmutE virus) was significantly attenuated for neurovirulence. To attenuate WNmutE virus further, we introduced five substitution mutations into the envelope (env) gene segment in wild-type (wt) WN and WNmutE genomes, based on differences in the env gene sequence between the live Japanese encephalitis vaccine (SA14-14-2) and its virulent parent. The env gene mutations had an attenuating effect in the context of the wt WNV genome but only a marginal enhancing effect on the attenuation of WNmutE virus.
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