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A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus
- Source :
- J Infect Dis
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- 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 (Stinggt/gt) had elevated viremia throughout the viremic stage and viral burden in feet transiently, with a normal type I IFN response. Stinggt/gt mice presented much greater foot swelling, joint damage, and immune cell infiltration than wild-type mice. Intriguingly, expression of interferon-γ and Cxcl10 was continuously upregulated by approximately 7 to 10-fold and further elevated in Stinggt/gt mice synchronously with arthritis progression. However, expression of chemoattractants for and activators of neutrophils, Cxcl5, Cxcl7, and Cxcr2 was suppressed in Stinggt/gt joints. These results demonstrate that STING deficiency leads to an aberrant chemokine response that promotes pathogenesis of CHIKV arthritis.
- Subjects :
- 0301 basic medicine
Chemokine
Arthritis
medicine.disease_cause
Virus
Major Articles and Brief Reports
Mice
03 medical and health sciences
0302 clinical medicine
Interferon
medicine
Animals
Immunology and Allergy
Viremia
Chikungunya
Mice, Knockout
biology
Membrane Proteins
DNA virus
medicine.disease
Immunity, Innate
eye diseases
Sting
030104 developmental biology
Infectious Diseases
Stimulator of interferon genes
Immunology
biology.protein
Chikungunya Fever
Chikungunya virus
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 223
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....1d773260a90c6c9ed862b7bbc39a56a8