Gene profiling of chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis

• Type of Material: Article
• Authors: Helder Nakaya, Emory University; Joy Gardner, University of Queensland; Yee-Suan Poo, University of Queensland; Lee Major, University of Queensland; Bali Pulendran, Emory University; Andreas Suhrbier, University of Queensland
• Language: English
• Date: 2012-11-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2012 by the American College of Rheumatology.
• Final Published Version (URL): http://dx.doi.org/10.1002/art.34631
• Title of Journal or Parent Work: Arthritis and Rheumatism
• ISSN: 0004-3591
• Volume: 64
• Issue: 11
• Start Page: 3553
• End Page: 3563
• Grant/Funding Information: Supported by a grant from the International Alliance Program of the Government of Queensland for collaboration between the Australian Centre for Vaccine Development and Emory Vaccine Center.; Dr. Nakaya was recipient of a travel award from the Australian Centre for Vaccine Development.
• Keywords: DISEASE; ALPHAVIRAL ARTHRITIS; INNATE IMMUNITY; INFECTION; ACUTE-PHASE; MICE; ROSS-RIVER-VIRUS; Life Sciences & Biomedicine; Science & Technology; CELLS; THERAPY; Rheumatology; MYOSITIS
• Research Categories: Health Sciences, Immunology

Abstract

Objective Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a chronic debilitating polyarthralgia/polyarthritis, for which current treatments are often inadequate. To assess whether new drugs being developed for rheumatoid arthritis (RA) might find utility in the treatment of alphaviral arthritides, we sought to determine whether the inflammatory gene expression signature of CHIKV arthritis shows any similarities with RA or collagen-induced arthritis (CIA), a mouse model of RA. Methods Using a recently developed animal model of CHIKV arthritis in adult wild-type mice, we generated a consensus CHIKV arthritis gene expression signature, which was used to interrogate publicly available microarray studies of RA and CIA. Pathway analyses were then performed using the overlapping gene signatures. Results Gene set enrichment analysis showed that there was a highly significant overlap in the differentially expressed genes in the CHIKV arthritis model and in RA. This concordance also increased with the severity of RA, as measured by the inflammation score. A highly significant overlap was also seen between CHIKV arthritis and CIA. Pathway analysis revealed that the overlap between these arthritides was spread over a range of different inflammatory processes. Involvement of T cells and interferon-γ (IFNγ) in CHIKV arthritis was confirmed in studies of MHCII-deficient mice and IFNγ-deficient mice, respectively. Conclusion These results suggest that RA, a chronic autoimmune arthritis, and CHIKV disease, usually a self-limiting viral arthropathy, share multiple inflammatory processes. New drugs and biologic therapies being developed for RA may thus find application in the treatment of alphaviral arthritides.