Mouse study reveals potential drug target for arthritis caused by chikungunya virus

February 16, 2017
Granzyme A emerges to be a major driver of chikungunya virus arthritis. Credit: Wilson et al. (2017)

An immune system proteinase called granzyme A appears to promote arthritic inflammation in mice infected with chikungunya virus, scientists report in a new PLOS Pathogens study. The study also suggested that granzyme A could serve as a potential target for new drugs to treat chikungunya and related viral arthritides in people.

Chikungunya is transmitted by mosquitoes, with a recent epidemic causing millions of cases globally. While it is rarely fatal, chikungunya can cause severe, chronic polyarthritis (inflammation in multiple joints) and/or polyarthralgia (pain in multiple joints). Current standard anti-inflammatory drug treatment can relieve these symptoms, but they are often not particularly effective.

To aid research into potential new treatments, Jane Wilson and Natalie Prow of QIMR Berghofer Medical Research Institute, Australia, and colleagues exploited an adult wild-type of infection and diseases previously developed by the group. In the new study, they use RNA-Seq technology to examine in detail the mouse inflammatory responses to infection. They found that genes activated in the mouse model closely mirrored genes known to be activated in infected humans, providing a level of validation of the model.

Particularly prominent in the RNA-Seq analysis was the up-regulation of a number of granzymes, a group of proteinases secreted by immune cells that were originally thought to be involved in killing (via apoptosis) virus infected cells or other target cells. However, an emerging consensus supported by the new PLOS Pathogens study, is that some granzymes (particularly granzyme A and K) have a role in promoting inflammation.

Exploring further, the scientists showed that mice missing the granzyme A gene, when infected with chikungunya virus, experienced dramatically less foot swelling and arthritis. Furthermore, treating mice with a granzyme A inhibitor also significantly reduced foot swelling and arthritis.

They also found elevated granzyme A levels in blood samples taken from non-human primates infected with chikungunya, as well as from human chikungunya patients. Overall the findings suggest that granzyme A could serve as a potential drug target for anti-inflammatory treatments for chikungunya—and perhaps also for other inflammatory diseases. Further research will be needed to explore this potential and determine how well the new findings can be extended from mice to humans.

Explore further: Drug combination effective against chikungunya arthritis in mice

More information: Wilson JAC, Prow NA, Schroder WA, Ellis JJ, Cumming HE, Gearing LJ, et al. (2017) RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation. PLoS Pathog 13(2): e1006155. DOI: 10.1371/journal.ppat.1006155

Related Stories

Drug combination effective against chikungunya arthritis in mice

February 1, 2017
Combining a drug for rheumatoid arthritis with one that targets the chikungunya virus can eliminate the signs of chikungunya arthritis in mice in the disease's earliest stage, according to researchers at Washington University ...

Putting a block on inflammation

December 16, 2015
Increasing the proportion of an anti inflammatory immune cell subtype can reduce damage to joints in mice infected with Chikungunya virus, research by A*STAR reveals. These findings are significant for the potential treatment ...

Researchers identify mechanism in chikungunya virus that controls infection and severity

January 30, 2017
Researchers led by the Johns Hopkins Bloomberg School of Public Health have identified a mechanism by which the chikungunya virus infects healthy cells and controls how severe the disease it causes will be, a mechanism they ...

Confirmed cases of chikungunya soar in Brazil

November 24, 2016
Brazil's Health Ministry says that cases of chikungunya are soaring this year in Latin America's biggest country.

Researchers develop first chikungunya vaccine from virus that does not affect people

December 19, 2016
Researchers from The University of Texas Medical Branch at Galveston have developed the first vaccine for chikungunya fever made from an insect-specific virus that doesn't have any effect on people, making the vaccine safe ...

Chikungunya virus shuts down infected cells

December 17, 2014
Researchers from Wageningen University, part of Wageningen UR, in collaboration with colleagues from Leiden University and a research team in Australia, have revealed how chikungunya virus blocks essential processes in infected ...

Recommended for you

Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections

September 22, 2017
Group A Streptococcus bacteria cause a variety of illnesses that range from mild nuisances like strep throat to life-threatening conditions including pneumonia, toxic shock syndrome and the flesh-eating disease formally known ...

Ecosystem approach makes urinary tract infection more treatable

September 22, 2017
The biological term 'ecosystem' is not usually associated with urinary tract infections, but this should change according to Wageningen scientists.

Residents: Frontline defenders against antibiotic resistance?

September 22, 2017
Antibiotic resistance continues to grow around the world, with sometimes disastrous results. Some strains of bacteria no longer respond to any currently available antibiotic, making death by infections that were once easily ...

Individualized diets for irritable bowel syndrome better than placebo

September 21, 2017
Patients with irritable bowel syndrome who follow individualized diets based on food sensitivity testing experience fewer symptoms, say Yale researchers. Their study is among the first to provide scientific evidence for this ...

Superbug's spread to Vietnam threatens malaria control

September 21, 2017
A highly drug resistant malaria 'superbug' from western Cambodia is now present in southern Vietnam, leading to alarming failure rates for dihydroartemisinin (DHA)-piperaquine—Vietnam's national first-line malaria treatment, ...

A dose of 'wait-and-see' reduces unnecessary antibiotic use

September 21, 2017
Asking patients to take a 'wait-and-see' approach before having their antibiotic prescriptions filled significantly reduces unnecessary use, a University of Queensland study has shown.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.