A combination of naturally occurring mutations in North American West Nile virus nonstructural protein genes and in the 3' untranslated region alters virus phenotype |
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| Authors: | Davis C Todd Galbraith Sareen E Zhang Shuliu Whiteman Melissa C Li Li Kinney Richard M Barrett Alan D T |
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| Affiliation: | Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA. |
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| Abstract: | We previously reported mutations in North American West Nile viruses (WNVs) with a small-plaque (sp), temperature-sensitive (ts), and/or mouse-attenuated (att) phenotype. Using an infectious clone, site-directed mutations and 3' untranslated region (3'UTR) exchanges were introduced into the WNV NY99 genome. Characterization of mutants demonstrated that a combination of mutations involving the NS4B protein (E249G) together with either a mutation in the NS5 protein (A804V) or three mutations in the 3'UTR (A10596G, C10774U, A10799G) produced sp, ts, and/or att variants. These results suggested that the discovery of North American WNV-phenotypic variants is rare because of the apparent requirement of concurrent polygenic mutations. |
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