title: A combination of naturally occurring mutations in North American West Nile virus nonstructural protein genes and in the 3' untranslated region alters virus phenotype.
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.
authors: Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
authors: C Todd
authors: CT
authors: Davis
authors: Sareen E
authors: SE
authors: Galbraith
authors: Shuliu
authors: S
authors: Zhang
authors: Melissa C
authors: MC
authors: Whiteman
authors: Li
authors: L
authors: Li
authors: Richard M
authors: RM
authors: Kinney
authors: Alan D T
authors: AD
authors: Barrett
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009656:North America; D010641:Phenotype; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014902:West Nile virus / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D020413:3' Untranslated Regions; D017361:Viral Nonstructural Proteins