More virulent form of West Nile Virus investigated in Australia

A micrograph of the West Nile Virus, appearing in yellow. Image: Cynthia Goldsmith, P.E. Rollin, USCDCP, public domain

The strain of West Nile Virus that has historically circulated in Australia is considered more benign than other strains circulating globally, but in 2011 the picture changed.

A more virulent strain emerged, with infections confirmed in about 1000 horses, 10 percent of whom died.

Researchers have now delved further into the nature of the new strain of the mosquito-borne virus, in particular investigating the inflammatory response it generates in cells.

In Australia, West Nile Virus was first isolated from Culex annulirostris mosquitoes in northern Queensland in 1960. It has most likely been a part of the country’s ecology for a long time.

Historically, it was called Kunjin virus, but was re-classified as a subtype of West Nile virus (WNVKUN).

WNVKUN can cause disease including encephalitis (brain inflammation) in humans and horses, but is generally considered less dangerous than other West Nile strains around the world.

WNVKUN is genetically similar across Australia due to the nature of its repeated dissemination from the tropical north of the country to southern interior regions by migrating wading birds after flooding rains.

However, in 2011 there was a serious outbreak of a mosquito-borne disease in Australia affecting about 1000 horses, resulting in neurological disease and death in 10% of cases.

“Despite the circulation of this virulent strain of WNVKUN, there was only a single human case around the time of the outbreak,” David Warrilow and his colleagues noted in the journal, BMC Infectious Diseases.

“The drivers of the emergence of this more virulent form of the disease are not entirely clear,” they said. They are likely to be multi-factorial and include viral fitness for its mosquito vector, and possibly other environmental factors.

So, what made the strain circulating more virulent?

Genetic sequencing at the time revealed the presence of virulence markers, but these were also present in older and less virulent strains, suggesting they could not be solely responsible.

Therefore, other unknown genome changes are likely to have contributed to the disease outbreak.

The study team set out to learn more about this virulent form.

For their research, they infected cells with either the virulent strain, dubbed NSW2012, or less pathogenic historical isolates, and their innate immune responses were compared by digital immune gene expression profiling, using two systems.

This allowed the researchers to assess the gene expression of 249 inflammation-associated genes.

Significant innate immune gene induction was observed in both systems, they noted.

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.”

The study team concluded that NSW2012 may have unique genetic characteristics that contributed to the outbreak.

The results, they said, were consistent with the possibility that the virulence of NSW2012 is underpinned by increased induction of inflammatory genes.

Discussing their findings, the researchers said West Nile infection can cause a range of symptoms from asymptomatic to lethal brain inflammation. The determinants of the disease outcome are likely a result of the complex interplay between the virus and the immune response of each host; however, this is not fully understood.

Their research had enabled them to determine if specific genes were induced by infection with more pathogenic strains.

“We found that, as with other strains of WNV, specific pathways were activated, and two genes were significantly more induced during infection with the virulent NSW2012 isolate.”

They said both systems used in the study will find future applications in understanding virus pathogenicity, and ultimately for the establishment of early warning systems for the detection of virulent emerging viruses.

The full study team comprised Bixing Huang, Nic West, Jelena Vider, Ping Zhang, Rebecca Griffiths, Ernst Wolvetang, Peter Burtonclay and Warrilow, from a range of Australian institutions.

Huang, B., West, N., Vider, J. et al. Inflammatory responses to a pathogenic West Nile virus strain. BMC Infect Dis 19, 912 (2019)

The study, published under a Creative Commons License, can be read here

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