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La Crosse virus (LACV) strains vary in their ability to cause disease. Some LACV strains show reduced neuroinvasiveness, impacting vaccine and therapeutic development for this pediatric encephalitis pathogen.

Keywords:
La Crosse virusarbovirusarbovirus pathogenesisencephalitic diseaseneuroinvasivenessneurovirulence

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Area of Science:

  • Virology
  • Neuroscience
  • Public Health

Background:

  • La Crosse virus (LACV) is a significant cause of pediatric viral encephalitis in North America.
  • Previous research on LACV pathogenesis primarily focused on lineage I strains, neglecting inter- and intra-lineage comparisons.

Purpose of the Study:

  • To investigate the differences in neurovirulence and neuroinvasiveness among various LACV strains representing all three lineages.
  • To test the hypothesis that certain LACV strains are attenuated, exhibiting reduced neuroinvasiveness.

Main Methods:

  • Comparison of four LACV strains from distinct lineages.
  • Utilized three distinct murine models to assess neurovirulence and neuroinvasiveness.
  • Evaluated mortality rates and viral spread within the central nervous system.

Main Results:

  • A lineage I strain demonstrated the highest lethality across all models (>50% mortality).
  • Other strains exhibited significant mortality (>50%) only in the suckling mouse neurovirulence model.
  • While neurovirulence was similar, neuroinvasive capacities varied significantly among strains.
  • Lineage III strains displayed differing pathogenesis, with contemporary isolates showing reduced neuroinvasiveness compared to an ancestral strain.

Conclusions:

  • LACV strains exhibit considerable variation in their pathogenic potential.
  • Strain-specific differences in pathogenesis are crucial for accurately evaluating the efficacy of vaccines and therapeutics against LACV.