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Journal of virology
Jun, 2010;84 (12): 5909-22.

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

Georgi Hristov, Melanie Krämer, Junwei Li, Nazim El-Andaloussi, Rodrigo Mora, Laurent Daeffler, Hanswalter Zentgraf, Jean Rommelaere, Antonio Marchini
Author Information
  1. Georgi Hristov: Infection and Cancer Program, German Cancer Research Center (DKFZ) and Inserm U701, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
PMID: 20375165 DOI: 10.1128/JVI.01797-09

Abstract

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.

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MeSH Term

Apoptosis
Cell Cycle
Cell Line
DNA Damage
H-1 parvovirus
Humans
Parvoviridae Infections
Reactive Oxygen Species
Viral Nonstructural Proteins

Chemicals

Reactive Oxygen Species
Viral Nonstructural Proteins
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 6

Word Cloud

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