Attenuated West Nile viruses bearing 3′SL and envelope gene substitution mutations
Li Yua b✉, Joseph Robert Putnakc, Alexander G. Pletnevd, Lewis J. Markoffb
- aLaboratory of Vector-borne Virus Diseases, Division of Viral Products, FDA, Bethesda, MD 20892, USA. Li.Yu@fda.hhs.gov
- bLaboratory of Vector-borne Virus Diseases, Division of Viral Products, FDA, Bethesda, MD 20892, United States
- cWalter Reed Army Institute of Research, Division of Communicable Diseases and Immunology, Silver Spring, MD 20910, United States
- dLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States
- ✉Corresponding author
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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.
TL;DRFive substitution mutations into the envelope (env) gene segment in wild-type WN and WNmutE genomes were introduced based on differences in the env gene sequence between the live Japanese encephalitis vaccine (SA14-14-2) and its virulent parent. (Semantic Scholar)