Inflammatory responses to a pathogenic West Nile virus strain

Area of Science:

• Virology
• Immunology
• Neuroscience

Background:

• West Nile virus (WNV), historically Kunjin virus (WNV_KUN), is endemic to Australia.
• WNV_KUN was considered less virulent globally until a more pathogenic strain emerged in 2011.
• This emergence coincided with an equine arboviral disease outbreak in Australia.

Purpose of the Study:

• Investigate the emergence of a virulent WNV phenotype.
• Understand the mechanisms of WNV pathogenicity.
• Compare innate immune responses to virulent and less pathogenic WNV strains.

Main Methods:

• Infection of SK-N-SH neuroblastoma cells and iPSC-derived neuronal cells with WNV strains.
• Digital immune gene expression profiling to compare innate immune responses.
• Pathway analysis of inflammation-associated genes.

Main Results:

• Significant innate immune gene induction observed in both cell systems.
• The virulent NSW2012 WNV isolate induced higher IL-8 and CCL2 gene expression.
• Pathway analysis indicated generally higher inflammation in NSW2012-infected cells, but not in neuronal cultures.

Conclusions:

• The NSW2012 WNV isolate may possess unique genetic traits driving its virulence.
• Increased induction of inflammatory genes likely underpins the enhanced virulence of NSW2012.
• Differential host responses may influence WNV pathogenicity in different cell types.