A schizont-derived protein, TpSCOP, is involved in the activation of NF-κB in Theileria parva-infected lymphocytes. uri icon

abstract

  • Theileria parva is a tick-transmitted intracellular protozoan parasite that causes East Coast fever, a fatal bovine lymphoproliferative disease. The molecular mechanisms that underlie host cell transformation by T. parva schizonts have been studied extensively, and it is known that the nuclear factor-kappa B (NF-kappa B) is activated in schizont-infected cells, making T. parva-transformed cells resistant to apoptosis. However, the mechanism by which the parasite triggers the activation of NF-kappa B remains enigmatic. In the present study, we biochemically characterized a novel protein, which we termed TpSCOP (T. parva schizont-derived cytoskeleton-binding protein), which is expressed in the schizont stage of T. parva. TpSCOP was shown to interact with F-actin in vitro. Expression of TpSCOP in a murine lymphocytic cell line resulted in the activation of NF-kappa B signaling pathways, leading to apoptosis resistance. The activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), was also detected. Furthermore, the introduction of TpSCOP into T. parva-infected cells also enhanced the activation of NF-kappa B. This is the first report to demonstrate that a parasite-derived molecule has the ability to activate the host NF-kappa B pathway. Based on these results, TpSCOP likely plays an important role in apoptosis inhibition during Theileria infection. (C) 2010 Elsevier B.V. All rights reserved.
  • Theileria parva is a tick-transmitted intracellular protozoan parasite that causes East Coast fever, a fatal bovine lymphoproliferative disease. The molecular mechanisms that underlie host cell transformation by T. parva schizonts have been studied extensively, and it is known that the transcription factor NF-?B is activated in schizont?infected cells, which makes the T. parva-transformed cells resistant to apoptosis. However, the mechanism by which the parasite triggers the activation of NF-?B remains enigmatic. In the present study, we biochemically characterized a novel protein, which we termed TpSCOP, which is expressed in the schizont stage of T. parva. TpSCOP was shown to interact with F-actin in vitro. Expression of TpSCOP in a murine lymphocytic cell line resulted in the activation of NF-?B signaling pathways, leading to apoptosis resistance. The activation of MAPKs, including ERK and JNK, were also detected. Furthermore, the introduction of TpSCOP into T. parva-infected cells also enhanced the activation of NF-?B. This is the first report to demonstrate that parasite-derived molecule has the ability to activate the host NF-?B pathway. Based on these results, TpSCOP likely plays an important role in apoptosis inhibition during Theileria infection

publication date

  • 2010
  • 2010
  • 2010