Public health

Enzyme a potential target in chikungunya arthritis

New research has revealed a potential drug target for chikungunya related arthritis.

Professor Andreas Suhrbier, head of the Inflammation Biology Laboratory at QIMR Berghofer, told the limbic it was previously thought an interferon response drove the inflammation seen in chikungunya arthritis.

However his research team has found the protease granzyme A is the major player driving the inflammation.

“This is certainly true for chikungunya but there are also hints that it is true for other diseases such as Ross River virus and rheumatoid arthritis.”

“Chikungunya arthritis and rheumatoid arthritis share a remarkably large number of inflammatory pathways,” Professor Suhrbier said.

The research published recently in PLOS Pathogens, pulls together findings in mice, humans and other primates.

Experimental studies in a mouse model of chikungunya infection and arthritis showed that animals deficient in granzyme A had a marked reduction in swelling and less cellular infiltrates in their feet than other animals.

Further studies showed a granzyme A inhibitor could significantly reduce foot swelling but not viraemia.

While other granzymes have an important function in cell death, Professor Suhrbier said granzyme A behaves more like a cytokine.

“There is now compelling evidence the chikungunya is not killing cells but instead promotes inflammation. It is up-regulated in infections including cytomegalovirus, HIV, malaria and others, circulates in the blood at high levels and is biologically active.”

He said granzymes were difficult to inhibit without off-target toxicity but it might be possible to target the protease activated receptor 1 (PAR1) that granzyme A activates.

“The next step is to see if anti-PAR1 drugs are useful in Ross River virus, chikungunya and arthritides.”

The chikungunya virus is closely related to the Ross River and Barmah Forest viruses but often causing more severe disease. It is widespread across Africa, Asia, Europe and America and can be transmitted by the Aedes aegypti mosquito, which is found in Queensland.

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