Through its nonstructural protein NS1, parvovirus H-1 induces apoptosis via accumulation of reactive oxygen species.

  • Laboratory of Oncolytic-Virus-Immuno-Therapeutics
June 01, 2010 By:
  • Hristov G
  • Kramer M
  • Li J
  • El-Andaloussi N
  • Mora R
  • Daeffler L
  • Zentgraf H
  • Rommelaere J
  • Marchini A.

The rat parvovirus H-1 (H-1PV) attracts high attention as an anticancer agent, because it is not pathogenic for humans and has oncotropic and oncosuppressive properties. The viral nonstructural NS1 protein is thought to mediate H-1PV cytotoxicity, but its exact contribution to this process remains undefined. In this study, we analyzed the effects of the H-1PV NS1 protein on human cell proliferation and cell viability. We show that NS1 expression is sufficient to induce the accumulation of cells in G(2) phase, apoptosis via caspase 9 and 3 activation, and cell lysis. Similarly, cells infected with wild-type H-1PV arrest in G(2) phase and undergo apoptosis. Furthermore, we also show that both expression of NS1 and H-1PV infection lead to higher levels of intracellular reactive oxygen species (ROS), associated with DNA double-strand breaks. Antioxidant treatment reduces ROS levels and strongly decreases NS1- and virus-induced DNA damage, cell cycle arrest, and apoptosis, indicating that NS1-induced ROS are important mediators of H-1PV cytotoxicity.

2010 Jun. J Virol.84(12):5909-22. Epub 2010 Apr 7.
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