Inflammatory responses to a pathogenic West Nile virus strain

Bixing Huang,Ernst Wolvetang,Peter Burtonclay,Jelena Vider,Ping Zhang,Rebecca E Griffiths,David Warrilow,Nic West

doi:10.1186/s12879-019-4471-8

Bixing Huang, Ernst Wolvetang + Show 6 more

Open Access

https://doi.org/10.1186/s12879-019-4471-8

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Abstract

BackgroundWest Nile virus (WNV) circulates across Australia and was referred to historically as Kunjin virus (WNVKUN). WNVKUN has been considered more benign than other WNV strains circulating globally. In 2011, a more virulent form of the virus emerged during an outbreak of equine arboviral disease in Australia.MethodsTo better understand the emergence of this virulent phenotype and the mechanism by which pathogenicity is manifested in its host, cells were infected with either the virulent strain (NSW2012), or less pathogenic historical isolates, and their innate immune responses compared by digital immune gene expression profiling. Two different cell systems were used: a neuroblastoma cell line (SK-N-SH cells) and neuronal cells derived from induced pluripotent stem cells (iPSCs).ResultsSignificant innate immune gene induction was observed in both systems. The NSW2012 isolate induced higher gene expression of two genes (IL-8 and CCL2) when compared with cells infected with less pathogenic isolates. Pathway analysis of induced inflammation-associated genes also indicated generally higher activation in infected NSW2012 cells. However, this differential response was not paralleled in the neuronal cultures.ConclusionNSW2012 may have unique genetic characteristics which contributed to the outbreak. The data herein is consistent with the possibility that the virulence of NSW2012 is underpinned by increased induction of inflammatory genes.

Highlights

West Nile virus (WNV) circulates across Australia and was referred to historically as Kunjin virus (WNVKUN)
Detection of gene expression in WNV infected human neuroblastoma cells To determine the optimum time post-infection for induction of inflammation associated genes in infected neuroblastoma cells (SK-N-SH line), the cells were infected with the prototype WNVKUN strain (MRM16) and the cells harvested at different time points post-infection
To test that the cells were capable of responding to immunostimulants, poly(I:C) and LPS were used and gene expression of innate immune responses measured (Additional file 3)

Summary

Introduction

West Nile virus (WNV) circulates across Australia and was referred to historically as Kunjin virus (WNVKUN). WNVKUN has been considered more benign than other WNV strains circulating globally. In 2011, a more virulent form of the virus emerged during an outbreak of equine arboviral disease in Australia. WNVKUN can cause disease including encephalitis in human and horses, but is generally considered more benign than other WNV strains circulating globally [2]. Despite the circulation of this virulent strain of WNVKUN, there was only a single human case around the time of the outbreak [7]. The drivers of the emergence of this more virulent form of the disease are not entirely clear, are likely to be multi-factorial and include viral fitness for its Cx. annulirostris vector [8], and possibly other environmental factors. Other unknown genome changes are likely to have contributed to the disease outbreak

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