Through its nonstructural protein NS1, parvovirus H-1 induces apoptosis via accumulation of reactive oxygen species.
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.
Hristov
Georgi
G
Infection and Cancer Program, German Cancer Research Center (DKFZ) and Inserm U701, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
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
D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D004249:DNA Damage; D052661:H-1 parvovirus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010322:Parvoviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology* / Q000821:virology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
D017382:Reactive Oxygen Species; D017361:Viral Nonstructural Proteins