title: Canine parvovirus NS1 induced apoptosis involves mitochondria, accumulation of reactive oxygen species and activation of caspases.
abstract: The non-structural protein (NS1) of parvoviruses plays an important role in viral replication and is thought to be responsible for inducing cell death. However, the detailed mechanism and the pathways involved in canine parvovirus type 2 NS1 (CPV2.NS1) induced apoptosis are not yet known. In the present study, we report that expression of CPV2.NS1 in HeLa cells arrests cells in G1 phase of the cell cycle and the apoptosis is mitochondria mediated as indicated by mitochondrial depolarization, release of cytochrome-c and activation of caspase 9. Treatment of cells with caspase 9 inhibitor Z-LEHD-FMK reduced the induction of apoptosis significantly. We also report that expression of CPV2.NS1 causes accumulation of reactive oxygen species (ROS) and treatment with an antioxidant reduces the ROS levels and the extent of apoptosis. Our results provide an insight into the mechanism of CPV2.NS1 induced apoptosis, which might prove valuable in developing NS1 protein as an oncolytic agent.
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India. Electronic address: shishirgupta.biotech@gmail.com.
authors.forename: Shishir Kumar
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India.
authors.forename: Aditya Prasad
authors.initials: AP
authors.lastname: Sahoo
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India.
authors.forename: Nighil
authors.initials: N
authors.lastname: Rosh
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Gandham
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India.
authors.forename: Lovleen
authors.initials: L
authors.lastname: Saxena
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India.
authors.forename: D R
authors.initials: DR
authors.lastname: Harish
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar-243122, India. Electronic address: aktiwari63@yahoo.com.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Tiwari
mesh_terms: D017209:Apoptosis; D053453:Caspase 9 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D017993:Parvovirus, Canine / Q000472:pathogenicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D017361:Viral Nonstructural Proteins; D053453:Caspase 9
keywords: Apoptosis; Cancer; Gene therapy; NS1; Parvovirus