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Journal of Virology, June 2007, p. 6111-6116, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02387-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Combination of Naturally Occurring Mutations in North American West Nile Virus Nonstructural Protein Genes and in the 3' Untranslated Region Alters Virus Phenotype{triangledown}

C. Todd Davis,1,{dagger} Sareen E. Galbraith,1 Shuliu Zhang,2 Melissa C. Whiteman,1 Li Li,1 Richard M. Kinney,6 and Alan D. T. Barrett1,3,4,5*

Department of Pathology,1 Department of Microbiology and Immunology,2 Center for Biodefense and Emerging Infectious Diseases,3 Sealy Center for Vaccine Development,4 Institute for Human Infections and Immunity, University of Texas Medical Branch, 301 University Blvd., Galveston, Texas 77555,5 Arboviral Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Fort Collins, Colorado6

Received 31 October 2006/ Accepted 5 March 2007

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.

* Corresponding author. Mailing address: Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555. Phone: (409) 772-6662. Fax: (409) 772-2500. E-mail: abarrett{at}utmb.edu

{triangledown} Published ahead of print on 21 March 2007.

{dagger} Present address: Molecular Virology and Vaccines Branch, Influenza Division, CDC, 1600 Clifton Road N.E., MS-G16, Atlanta, GA 30333.

Journal of Virology, June 2007, p. 6111-6116, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02387-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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