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

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.

SUBMITTER: Hristov G

PROVIDER: S-EPMC2876649 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Hristov Georgi G Krämer Melanie M Li Junwei J El-Andaloussi Nazim N Mora Rodrigo R Daeffler Laurent L Zentgraf Hanswalter H Rommelaere Jean J Marchini Antonio A

Journal of virology 20100407 12

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 ...[more]

PMID: 20375165

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

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

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