Open AccessA Combination of Naturally Occurring Mutations in North American West Nile Virus Nonstructural Protein Genes and in the 3′ Untranslated Region Alters Virus Phenotype
Author(s) -
C. Todd Davis,
Sareen E. Galbraith,
Shuliu Zhang,
Melissa C. Whiteman,
Li Li,
Richard M. Kinney,
Alan D.T. Barrett
Publication year - 2007
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02387-06
Subject(s) - biology , gene , untranslated region , genetics , mutation , phenotype , mutant , virology , three prime untranslated region , genome , five prime untranslated region , clone (java method) , virus , rna
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) producedsp ,ts , and/oratt variants. These results suggested that the discovery of North American WNV-phenotypic variants is rare because of the apparent requirement of concurrent polygenic mutations.