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Chikungunya: Pain Caused by the Immune System

​Joint damage in people infected with chikungunya remains poorly understood. Scientists from the CEA François-Jacob Institute and their partners have identified an actor of the antiviral immune response whose inhibition paradoxically reduces the severity of the symptoms.

Published on 13 March 2017

Since it reappeared on the African continent in 2004 and then on Réunion Island in 2005, chikungunya has spread to Asia, Europe and more recently the Americas, causing many epidemics with several million cases in less than a decade. Transmitted to humans by the bite of an infected tiger mosquito (genus Aedes), this virus causes painful joint damage that is often very disabling, lasting for several months, even years, in 10 to 30% of cases. There is currently no available vaccine and the current treatments are limited to just affecting symptoms.

A team from the François-Jacob Biology Institute has developed a non-human primate model (NHP) of the chikungunya disease and has teamed up with an Australian team[1] for the design and study of a rodent model, in which they studied the expression of the genes of the immune response during the acute and chronic stages of the disease. "We first observed that, in agreement with our data related to the NHP model, the rodent model reproduces the immune response observed in humans, and notably the innate response," said Pierre Roques, a researcher at the François-Jacob Institute. "Then we sought to identify the profile of the inflammatory response in relation to joint damage that is a result of the infection." The biologists have pointed to the abnormally high amount of the granzyme A protein. This protein is involved in the innate and adaptive response of the body by degrading the infected cells. "Although granzyme A is useful to the organism, as it helps it get rid of the intruders, it becomes deleterious when in excessive amounts," said Roques. "An excessive amount of this protein maintains the local inflammation, generates joint symptoms and allows the virus to continue its progression." The researchers found an excessive amount of this protein in the NHP and in individuals infected with the chikungunya virus. The Janus effect[2] of granzyme A was confirmed using inhibitors. "The inhibition of granzyme A led to a significant reduction of joint swelling," Roque added. The results, therefore, point to a new target to treat the patients infected with the chikungunya virus.

[1] From the QIMR Berghofer Medical Research Institute.

[2] In Roman mythology, Janus is a god depicted with two faces looking in opposite directions.

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