A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus

The stimulator of interferon gene (STING) pathway controls both DNA and RNA virus infection. STING is essential for induction of innate immune responses during DNA virus infection, while its mechanism against RNA virus remains largely elusive. We show that STING signaling is crucial for restricting chikungunya virus infection and arthritis pathogenesis. Sting-deficient mice (Sting(gt/gt)) had elevated viremia throughout the viremic stage and viral burden in feet transiently, with a normal type I IFN response. Sting(gt/gt) mice presented much greater foot swelling, joint damage, and immune cell infiltration than wild-type mice. Intriguingly, expression of interferon-gamma and Cxcl10 was continuously upregulated by approximately 7 to 10-fold and further elevated in Sting(gt/gt) mice synchronously with arthritis progression. However, expression of chemoattractants for and activators of neutrophils, Cxcl5, Cxcl7, and Cxcr2 was suppressed in Sting(gt/gt) joints. These results demonstrate that STING deficiency leads to an aberrant chemokine response that promotes pathogenesis of CHIKV arthritis. Using a mouse model, we found that Sting deficiency resulted in increased chikungunya virus infection, inflammation in the footpad and joint, as well as interferon-gamma and Cxcl10 expression in the joint.

Automated summary

This study demonstrates the crucial role of STING signaling in restricting chikungunya virus infection and arthritis pathogenesis. Sting deficiency leads to increased viral burden, exacerbated arthritis, and upregulation of certain chemokines while other chemokines are suppressed in the joints.