A combination of naturally occurring mutations in North American West Nile virus nonstructural protein genes and in the 3' untranslated region alters virus phenotype.
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.
Davis
C Todd
CT
Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
Galbraith
Sareen E
SE
Zhang
Shuliu
S
Whiteman
Melissa C
MC
Li
Li
L
Kinney
Richard M
RM
Barrett
Alan D T
AD
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
D020413:3' Untranslated Regions; D017361:Viral Nonstructural Proteins