کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5822652 1117964 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Protein kinase inhibitors that inhibit induction of lytic program and replication of Epstein-Barr virus
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Protein kinase inhibitors that inhibit induction of lytic program and replication of Epstein-Barr virus
چکیده انگلیسی

Signaling pathways mediating Epstein-Barr virus (EBV) reactivation by Ag-bound B-cell receptor (BCR) were analyzed using a panel of 80 protein kinase inhibitors. Broad range protein kinase inhibitors Staurosporine, K252A, and PKC-412 significantly reduced the EBV genome copy numbers measured 48 h after reactivation perhaps due to their higher toxicity. In addition, selected inhibitors of the phosphatidylinositol-3-kinase (PI3K), protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways, glycogen synthase kinase 3β (GSK-3β), platelet-derived growth factor receptor-associated tyrosine kinase (PDGFRK), and epidermal growth factor receptor-associated tyrosine kinase (EGFRK) significantly reduced the EBV genome copy numbers. Of those, only U0126 and Erbstatin analog, which inhibit MAPK pathway and EGFRK, respectively, did not inhibit viral reactivation assessed by expression of the EBV early protein, EA-D. None of the tested compounds, except for K252A, affected the activity of the EBV-encoded protein kinase in vitro. These results show that EBV reactivation induced by BCR signaling is mainly mediated through PI3K and PKC, whereas MAPK might be involved in later stages of viral replication.

► Protein kinase inhibitors of PI3K, MAPK, and NF-κB pathways inhibit EBV replication. ► Out of 80 tested protein kinase inhibitors only K252A inhibited activity of EBV-PK. ► PI3K inhibitors seem to act during the reactivation; MAPK inhibitor U0126 acts later.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 96, Issue 3, December 2012, Pages 296-304
نویسندگان
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