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

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.