title: Deciphering the differential response of two human fibroblast cell lines following Chikungunya virus infection.
abstract: BACKGROUND
  Chikungunya virus (CHIKV) is an arthritogenic member of the Alphavirus genus (family Togaviridae) transmitted by Aedes mosquitoes. CHIKV is now known to target non hematopoietic cells such as epithelial, endothelial cells, fibroblasts and to less extent monocytes/macrophages. The type I interferon (IFN) response is an early innate immune mechanism that protects cells against viral infection. Cells express different pattern recognition receptors (including TLR7 and RIG-I) to sense viruses and to induce production of type I IFNs which in turn will bind to their receptor. This should result in the phosphorylation and translocation of STAT molecules into the nucleus to promote the transcription of IFN-stimulated antiviral genes (ISGs). We herein tested the capacity of CHIKV clinical isolate to infect two different human fibroblast cell lines HS 633T and HT-1080 and we analyzed the resulting type I IFN innate immune response.
  
  
  METHODS
  Indirect immunofluorescence and quantitative RT-PCR were used to test for the susceptibility of both fibroblast cell lines to CHIKV.
  
  
  RESULTS
  Interestingly, the two fibroblast cell lines HS 633T and HT-1080 were differently susceptible to CHIKV infection and the former producing at least 30-fold higher viral load at 48 h post-infection (PI). We found that the expression of antiviral genes (RIG-I, IFN-β, ISG54 and ISG56) was more robust in the more susceptible cell line HS 633T at 48 h PI. Moreover, CHIKV was shown to similarly interfere with the nuclear translocation of pSTAT1 in both cell lines.
  
  
  CONCLUSIONS
  Critically, CHIKV can control the IFN response by preventing the nuclear translocation of pSTAT1 in both fibroblast cell lines. Counter-intuitively, the relative resistance of HT-1080 cells to CHIKV infection could not be attributed to more robust innate IFN- and ISG-dependent antiviral responses. These cell lines may prove to be valuable models to screen for novel mechanisms mobilized differentially by fibroblasts to control CHIKV infection, replication and spreading from cell to cell.
authors.affiliation: Immunopathology and Infection Research Grouping (IRG), EA4517, University of La Reunion, CHU Felix Guyon and CYROI, St Denis, La Reunion, France.
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Thon-Hon
authors.forename: Melanie
authors.initials: M
authors.lastname: Denizot
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Li-Pat-Yuen
authors.forename: Claude
authors.initials: C
authors.lastname: Giry
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Jaffar-Bandjee
authors.forename: Philippe
authors.initials: P
authors.lastname: Gasque
mesh_terms: D002460:Cell Line; D002646:Chikungunya virus / Q000276:immunology* / Q000472:pathogenicity*; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology*; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D019562:Viral Load
chemical_list: D007370:Interferon Type I