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

Nakaya, Helder I., Gardner, Joy, Poo, Yee-Suan, Major, Lee, Pulendran, Bali and Suhrbier, Andreas (2012) Gene profiling of chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis. Arthritis and Rheumatism, 64 11: 3553-3563. doi:10.1002/art.34631


Author Nakaya, Helder I.
Gardner, Joy
Poo, Yee-Suan
Major, Lee
Pulendran, Bali
Suhrbier, Andreas
Title Gene profiling of chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
1529-0131
Publication date 2012-11
Sub-type Article (original research)
DOI 10.1002/art.34631
Volume 64
Issue 11
Start page 3553
End page 3563
Total pages 11
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2013
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Article first published online: 27 October 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Public Health Publications
School of Chemistry and Molecular Biosciences
 
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