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标题：Activation of NF-κB in cells productively infected with HSV-1 depends on activated protein kinase R and plays no apparent role in blocking apoptosis
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作者：Brunella Taddeo ; Ting Rong Luo ; Weiran Zhang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：21
页码：12408-12413
DOI：10.1073/pnas.2034952100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Microarray data reported elsewhere indicated that herpes simplex virus 1 induces the up-regulation of nuclear factor {kappa}B (NF-{kappa}B)-regulated genes, including that of its inhibitor, I{kappa}B, consistent with the reports that wild-type virus induces the activation of NF-{kappa}B. In this report we show that activation of NF-{kappa}B in infected cells is linked to the activation of protein kinase R (PKR). Specifically: (i) PKR is activated in infected cells although the effects of the activated enzyme on protein synthesis are negated by the viral gene {gamma}134.5, which encodes a protein phosphatase 1 accessory factor that enables the dephosphorylation of the subunit of eukaryotic translation initiation factor 2. NF-{kappa}B is activated in wild-type murine embryonic fibroblasts but not in related PKR-null cells. (ii) In cells infected with a replication-competent {Delta}{gamma}134.5 mutant (R5104), but carrying a US11 gene expressed early in infection, eukaryotic translation initiation factor 2 is not phosphorylated, and in in vitro assays, PKR bound to the US11 protein is not phosphorylated on subsequent addition of double-stranded RNA. Here we report that this mutant does not activate PKR, has no effect on the accumulation of I{kappa}B, and does not cause the translocation of NF-{kappa}B in infected cells. (iii) One hypothesis advanced for the activation of NF-{kappa}B is that it blocks apoptosis induced by viral gene products. The replication-competent R5104 mutant does not induce the programmed cell's death. We conclude that in herpes simplex virus 1-infected cells, activation of NF-{kappa}B depends on activation of PKR and that NF-{kappa}B is not required to block apoptosis in productively infected cells.