Deciphering the differential response of two human fibroblast cell lines following Chikungunya virus infection

Virology Journal

Philippe Gasque²  Marie-Christine Jaffar-Bandjee¹  Claude Giry²  Ghislaine Li-Pat-Yuen¹  Melanie Denizot²  Vincent G Thon-Hon² 

[1] Microbiology/Virology Laboratory, CHU Felix Guyon of La Reunion, St Denis, La Reunion, France;Immunopathology and Infection Research Grouping (IRG), EA4517, University of La Reunion, CHU Felix Guyon and CYROI, St Denis, La Reunion, France

关键词: STAT-1;    TLR7;    RIG-I;    HT-1080;    HS 633T;    Type I IFN;    CHIKV;   

Others  :  1153744
DOI  :  10.1186/1743-422X-9-213

 received in 2011-11-21, accepted in 2012-08-29,  发布年份 2012

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2012 Thon-Hon et al.; licensee BioMed Central Ltd.

【 图 表 】

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