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Inhibition of nuclear factor κB activity by viral interferon regulatory factor 3 of Kaposi's sarcoma-associated herpesvirus

Oncogene volume 23, pages 6146–6155 (2004)Cite this article

Abstract

Nuclear factor-κB (NF-κB) is a transcription factor that plays an important role in the immune system and cell death. Many viral proteins modulate NF-κB to escape host immune surveillance, promote cell survival, and enhance viral replication. In the present study, we show that NF-κB activity is downmodulated by viral interferon regulatory factor 3 (vIRF3), which is encoded by Kaposi's sarcoma-associated herpesvirus open-reading frame K10.5. vIRF3 repressed NF-κB-dependent transcription in a dose-dependent manner and inhibited the activation of NF-κB induced by tumor necrosis factor (TNF)-α. In vivo studies showed vIRF3 inhibited IκB kinase β (IKKβ) activity, but not IKKα activity, resulting in reduced IκB phosphorylation. Immunofluorescence assays showed that vIRF3 interfered with nuclear translocation of NF-κB. In addition, consistent with the inhibition of NF-κB activity, vIRF3 sensitized cells to TNF-α-induced apoptosis. While vIRF3 interacts with IKKβ in vitro and in 293T cells, we were unable to demonstrate vIRF3–IKKβ interaction in BCBL-1 cells. Our results indicate that vIRF3 can regulate the host immune system and apoptosis via inhibition of NF-κB activity.

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Acknowledgements

We thank Dr Yuan Chang for the vIRF3/LANA2 cDNA and monoclonal antibody against vIRF3/LANA2. This work was supported in part by the National Research Laboratory Program of the Korea Institute of Science and Technology Evaluation and Planning (KISTEP), by the Molecular Medicine Research Group Program of KISTEP through the Biomedical Research Center at Korea Advanced Institute of Science and Technology, and by the BK21 Program of the Ministry of Education, Republic of Korea.

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  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea

    Taegun Seo, Junsoo Park, Chunghun Lim & Joonho Choe

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  1. Taegun Seo
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Correspondence to Joonho Choe.

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Seo, T., Park, J., Lim, C. et al. Inhibition of nuclear factor κB activity by viral interferon regulatory factor 3 of Kaposi's sarcoma-associated herpesvirus. Oncogene 23, 6146–6155 (2004). https://doi.org/10.1038/sj.onc.1207807

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