کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2178489 1549698 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The kinase inhibitor Sorafenib impairs the antiviral effect of interferon α on hepatitis C virus replication
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
The kinase inhibitor Sorafenib impairs the antiviral effect of interferon α on hepatitis C virus replication
چکیده انگلیسی

Recently, it was shown that the kinase inhibitor Sorafenib efficiently blocks HCV replication by inhibition of c-Raf. However, a longer treatment with higher doses of Sorafenib might be associated with adverse effects. Therefore, it was analysed whether a decreased dose of Sorafenib can be applied in combination with interferon α to obtain additive antiviral, but at the same time decreased adverse effects. However, Sorafenib abolishes the inhibitory effect of interferon α on HCV replication and vice versa. In order to reveal the underlying mechanisms, we observed that on the one hand IFNα activates c-Raf and thereby counteracts the inhibitory effect of Sorafenib on HCV replication that is based on the Sorafenib-dependent inhibition of c-Raf. On the other hand we found that the IFNα-induced PKR-phosphorylation depends on c-Raf. So, Sorafenib as a potent inhibitor of c-Raf prevents the IFNα-dependent PKR phosphorylation. Moreover, Sorafenib inhibits c-Raf-independent the phosphorylation of STAT1 resulting in an impaired induction of IFNα-dependent genes. Taken together, these data indicate that a combined application of Sorafenib and interferon α in order to obtain an antiviral effect is not useful since Sorafenib exerts an inhibitory effect on targets that are crucial for the transduction of interferon α-dependent antiviral response.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cell Biology - Volume 92, Issue 1, January 2013, Pages 12–20
نویسندگان
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