Several studies have demonstrated that HTLV-1 induces alteration of type I interferon (IFN-I) signalling. However, the role of innate immunity in HTLV-1 pathogenesis is not yet clearly understood. Conflicting results on the role of Tax-1 protein in altering IFN-I signaling have been reported: some in vitro studies provided evidence that Tax-1 expression can lead to constitutive IFN regulatory factor 3 (IRF3) activation, whereas other data indicated that IRF3 degradation is mediated by expression of Tax-1 and resulted in increased stability of SOCS1. In the present study we have investigated Tax-1 and Tax-2 roles in modifying IRF activation through the recruitment of IKKepsilon and TBK1, two related IkB kinase homologues that are essential for activation of IRF3 pathway. We have observed that both Tax-1 and Tax-2 co-immunoprecipitated with IKKepsilon in HEK293T transfected cells. However, the IRF3 factor was not detectable in Tax-1 immunocomplexes. The effect of overexpression of Tax proteins and IKKepsilon or TBK1 on the activation of IFN responsive elements has been analyzed in HEK293T transfected cells by measuring luciferase activity. Co-expression of Tax-1 and IKKepsilon, as well as co-expression of Tax-1 and TBK1, resulted in a significant increase of IRF mediated activation. These results support an active role of Tax-1 and Tax-2 proteins in IRF3 activation and their involvement in modifying the endogenous IFN pathway gene expression. This study is funded by AIRC-Cariverona.
Tax-1 interacts with IKKepsilon and modulates IRF-3 dependent promoter activity in transfected cells.
DIANI, ERICA;ROMANELLI, Maria
2012-01-01
Abstract
Several studies have demonstrated that HTLV-1 induces alteration of type I interferon (IFN-I) signalling. However, the role of innate immunity in HTLV-1 pathogenesis is not yet clearly understood. Conflicting results on the role of Tax-1 protein in altering IFN-I signaling have been reported: some in vitro studies provided evidence that Tax-1 expression can lead to constitutive IFN regulatory factor 3 (IRF3) activation, whereas other data indicated that IRF3 degradation is mediated by expression of Tax-1 and resulted in increased stability of SOCS1. In the present study we have investigated Tax-1 and Tax-2 roles in modifying IRF activation through the recruitment of IKKepsilon and TBK1, two related IkB kinase homologues that are essential for activation of IRF3 pathway. We have observed that both Tax-1 and Tax-2 co-immunoprecipitated with IKKepsilon in HEK293T transfected cells. However, the IRF3 factor was not detectable in Tax-1 immunocomplexes. The effect of overexpression of Tax proteins and IKKepsilon or TBK1 on the activation of IFN responsive elements has been analyzed in HEK293T transfected cells by measuring luciferase activity. Co-expression of Tax-1 and IKKepsilon, as well as co-expression of Tax-1 and TBK1, resulted in a significant increase of IRF mediated activation. These results support an active role of Tax-1 and Tax-2 proteins in IRF3 activation and their involvement in modifying the endogenous IFN pathway gene expression. This study is funded by AIRC-Cariverona.
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