Background/Purpose: Chikungunya virus (CHIKV) is an arthritogenic alphavirus that invades the joints and causes chronic arthritis in up to 60% of infected individuals. Over the last two years, approximately 2 million people have been infected with CHIKV in the Western Hemisphere. The symptoms and immunological features of CHIKV arthritis mimic phenotypes observed in patients with untreated rheumatoid arthritis. Interferon regulatory factors (IRF) including IRF5 contribute to anti-viral immunity, but polymorphisms leading to over-expression of IRF5 increase the risk of developing rheumatologic disease. Thus, we reasoned that IRF5 expression may modulate the pathogenesis of CHIKV infection including the risk of developing severe CHIKV arthritis.

Methods: IRF5 knockout mice and wild-type control animals were infected with a highly pathogenic La Reunion strain of CHIKV and then monitored for virus replication, spread, and clinical features of disease including joint swelling, cytokine production, and leukocyte infiltration.

Results:  We found that expression of IRF5 restricts CHIKV dissemination to distal joints, but at the expense of triggering more severe acute CHIKV arthritis. IRF5 expression was associated with enhanced cytokine production and leukocyte infiltration into the joints of infected animals.

Conclusion: IRF5 restricts CHIKV dissemination and promotes acute arthritis in mice. These findings suggest that over-expression of IRF5 in humans may limit the spread of arthritogenic alphaviruses to distal joints, but at the cost of promoting more severe clinical disease during the acute phase of infection.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/irf5-promotes-arthritis-but-restricts-virus-replication-and-spread-during-chikungunya-virus-infection/