Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains

David Beasley, Melissa C. Whiteman, Shuliu Zhang, Claire Y H Huang, Bradley S. Schneider, Darci R. Smith, Gregory D. Gromowski, Stephen Higgs, Richard M. Kinney, Alan Barrett

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

The introduction of West Nile virus (WNV) into North America has been associated with relatively high rates of neurological disease and death in humans, birds, horses, and some other animals. Previous studies identified strains in both genetic lineage 1 and genetic lineage 2, including North American isolates of lineage 1, that were highly virulent in a mouse neuroinvasion model, while other strains were avirulent or significantly attenuated (D. W. C. Beasley, L. Li, M. T. Suderman, and A. D. T. Barrett, Virology 296:17-23, 2002). To begin to elucidate the basis for these differences, we compared a highly virulent New York 1999 (NY99) isolate with a related Old World lineage 1 strain, An4766 (ETH76a), which is attenuated for mouse neuroinvasion. Genomic sequencing of ETH76a revealed a relatively small number of nucleotide (5.1%) and amino acid (0.6%) differences compared with NY99. These differences were located throughout the genome and included five amino acid differences in the envelope protein gene. Substitution of premembrane and envelope genes of ETH76a into a NY99 infectious clone backbone yielded a virus with altered in vitro growth characteristics and a mouse virulence phenotype comparable to ETH76a. Further site-specific mutagenesis studies revealed that the altered phenotype was primarily mediated via loss of envelope protein glycosylation and that this was associated with altered stability of the virion at mildly acidic pH. Therefore, the enhanced virulence of North American WNV strains compared with other Old World lineage 1 strains is at least partly mediated by envelope protein glycosylation.

Original languageEnglish (US)
Pages (from-to)8339-8347
Number of pages9
JournalJournal of Virology
Volume79
Issue number13
DOIs
StatePublished - Jul 2005

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West Nile virus
glycosylation
Glycosylation
Phenotype
phenotype
Virulence
mice
Amino Acids
Virology
proteins
North America
Site-Directed Mutagenesis
virulence
Virion
Horses
Birds
Nucleotides
Clone Cells
virology
amino acids

ASJC Scopus subject areas

  • Immunology

Cite this

Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains. / Beasley, David; Whiteman, Melissa C.; Zhang, Shuliu; Huang, Claire Y H; Schneider, Bradley S.; Smith, Darci R.; Gromowski, Gregory D.; Higgs, Stephen; Kinney, Richard M.; Barrett, Alan.

In: Journal of Virology, Vol. 79, No. 13, 07.2005, p. 8339-8347.

Research output: Contribution to journalArticle

Beasley, D, Whiteman, MC, Zhang, S, Huang, CYH, Schneider, BS, Smith, DR, Gromowski, GD, Higgs, S, Kinney, RM & Barrett, A 2005, 'Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains', Journal of Virology, vol. 79, no. 13, pp. 8339-8347. https://doi.org/10.1128/JVI.79.13.8339-8347.2005
Beasley, David ; Whiteman, Melissa C. ; Zhang, Shuliu ; Huang, Claire Y H ; Schneider, Bradley S. ; Smith, Darci R. ; Gromowski, Gregory D. ; Higgs, Stephen ; Kinney, Richard M. ; Barrett, Alan. / Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains. In: Journal of Virology. 2005 ; Vol. 79, No. 13. pp. 8339-8347.
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