Autor(es): Nakaya Helder I, Gardner Joy, Poo Yee-Suan, Major Lee, Pulendran Bali, Suhrbier Andreas

Resumo: 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. 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 - CIA. Pathway analyses were then performed using the overlapping gene signatures. Gene set enrichment analysis showed that there was a highly significant overlap in the differentially expressed genes in the CHIKV arthritis model - 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 - CIA. Pathway analysis revealed that the overlap between these arthritides was spread over a range of different inflammatory processes. Involvement of T cells - interferon-? (IFN?) in CHIKV arthritis was confirmed in studies of MHCII-deficient mice - IFN?-deficient mice, respectively. These results suggest that RA, a chronic autoimmune arthritis, - CHIKV disease, usually a self-limiting viral arthropathy, share multiple inflammatory processes. New drugs - biologic therapies being developed for RA may thus find application in the treatment of alphaviral arthritides.

Imprenta: Arthritis and Rheumatism, v. 64, n. 11, p. 3553-3563, 2012

Identificador do objeto digital: 10.1002/art.34631

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology

Data de publicação: 2012