title: Gene profiling of Chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  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.
authors: Emory Vaccine Center at Yerkes National Primate Research Center, Atlanta, Georgia, USA.
authors: Helder I
authors: HI
authors: Nakaya
authors: Joy
authors: J
authors: Gardner
authors: Yee-Suan
authors: YS
authors: Poo
authors: Lee
authors: L
authors: Major
authors: Bali
authors: B
authors: Pulendran
authors: Andreas
authors: A
authors: Suhrbier
mesh_terms: D018354:Alphavirus Infections / Q000150:complications / Q000235:genetics / Q000276:immunology; D000818:Animals; D001170:Arthritis, Infectious / Q000235:genetics / Q000276:immunology / Q000821:virology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000821:virology; D001208:Asia; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000276:immunology*; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D017508:Reunion; D013583:Synovial Membrane / Q000276:immunology; D059467:Transcriptome / Q000276:immunology*