Torque Teno Virus (SANBAN Isolate) ORF2 Protein Suppresses NF-κB Pathways via Interaction with IκB Kinases

  • Hong Zheng
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Linbai Ye
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Xiaonan Fang
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Baozong Li
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Yuhua Wang
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Xiaoxiao Xiang
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Lingbao Kong
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Wei Wang
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Yinchun Zeng
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Li Ye
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Zhenghui Wu
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Yinglong She
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China
  • Xiaolin Zhou
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China

抄録

<jats:title>ABSTRACT</jats:title><jats:p>Since the first discovery of Torque teno virus (TTV) in 1997, many researchers focused on its epidemiology and transcriptional regulation, but the function of TTV-encoded proteins remained unknown. The function of the TTV open reading frame (ORF) in the nuclear factor κB (NF-κB) pathway has not yet been established. In this study, we found for the first time that the TTV ORF2 protein could suppress NF-κB activity in a dose-dependent manner in the canonical NF-κB pathway. By Western blot analysis, we proved that the TTV ORF2 protein did not alter the level of NF-κB expression but prevented the p50 and p65 subunits from entering the nucleus due to the inhibition of IκBα protein degradation. Further immunoprecipitation assays showed that the TTV ORF2 protein could physically interact with IKKβ as well as IKKα, but not IKKγ. Luciferase assays and Western blot experiments showed that the TTV ORF2 protein could also suppress NF-κB activity in the noncanonical NF-κB pathway and block the activation and translocation of p52. Finally, we found that the TTV ORF2 protein inhibited the transcription of NF-κB-mediated downstream genes (interleukin 6 [IL-6], IL-8, and COX-2) through down-regulation of NF-κB. Together, these data indicate that the TTV ORF2 protein suppresses the canonical and noncanonical NF-κB pathways, suggesting that the TTV ORF2 protein may be involved in regulating the innate and adaptive immunity of organisms, contributing to TTV pathogenesis, and even be related to some diseases.</jats:p>

収録刊行物

  • Journal of Virology

    Journal of Virology 81 (21), 11917-11924, 2007-11

    American Society for Microbiology

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