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Genome sequence and attenuating mutations in West Nile virus isolate from Mexico

David W C Beasley1, C Todd Davis, Jose Estrada-Franco

  • 1University of Texas Medical Branch, Galveston, Texas 77555-0609, USA. d.beasley@utmb.edu

Emerging Infectious Diseases
|January 25, 2005
PubMed

Insights

A Mexican West Nile virus isolate, TM171-03, shows genetic differences from the NY99 prototype. Mutations in its E protein suggest an attenuating mutation may have emerged, impacting mouse virulence.

Area of Science:

  • Virology
  • Genomics
  • Molecular Biology

Background:

  • West Nile virus (WNV) poses a significant public health concern.
  • Understanding genetic variations in WNV isolates is crucial for tracking its evolution and virulence.
  • The NY99 prototype serves as a reference strain for WNV genetic comparisons.

Purpose of the Study:

  • To perform a complete genome sequence analysis of a Mexican West Nile virus isolate (TM171-03).
  • To compare the genetic makeup of TM171-03 with the NY99 prototype.
  • To investigate potential correlations between genetic mutations and viral virulence in mice.

Main Methods:

  • Whole-genome sequencing of the TM171-03 West Nile virus isolate.
  • Bioinformatic analysis to identify nucleotide and amino acid differences compared to the NY99 prototype.
  • Mouse virulence assays using plaque-purified variants of TM171-03 with specific mutations.

Main Results:

  • The complete genome sequence of TM171-03 revealed 46 nucleotide (0.42%) and 4 amino acid (0.11%) differences from the NY99 prototype.
  • Significant differences in mouse virulence were observed between plaque-purified variants of TM171-03.
  • Mutations within the E protein glycosylation motif were associated with observed virulence differences.

Conclusions:

  • The Mexican West Nile virus isolate TM171-03 exhibits distinct genetic characteristics compared to the NY99 prototype.
  • Emergence of an attenuating mutation within the E protein glycosylation motif is suggested by virulence studies.
  • Further research is warranted to fully elucidate the impact of these genetic variations on West Nile virus pathogenesis.

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