title: Induction of a Cellular DNA Damage Response by Porcine Circovirus Type 2 Facilitates Viral Replication and Mediates Apoptotic Responses.
abstract: Cellular DNA damage response (DDR) triggered by infection of DNA viruses mediate cell cycle checkpoint activation, DNA repair, or apoptosis induction. In the present study, infection of porcine circovirus type 2 (PCV2), which serves as a major etiological agent of PCV2-associated diseases (PCVAD), was found to elicit a DNA damage response (DDR) as observed by the phosphorylation of H2AX and RPA32 following infection. The response requires active viral replication, and all the ATM (ataxia telangiectasia-mutated kinase), ATR (ATM- and Rad3-related kinase), and DNA-PK (DNA-dependent protein kinase) are the transducers of the DDR signaling events in the PCV2-infected cells as demonstrated by the phosphorylation of ATM, ATR, and DNA-PK signalings as well as reductions in their activations after treatment with specific kinase inhibitors. Inhibitions of ATM, ATR, and DNA-PK activations block viral replication and prevent apoptotic responses as observed by decreases in cleaved poly-ADP ribose polymerase (PARP) and caspase-3 as well as fragmented DNA following PCV2 infection. These results reveal that PCV2 is able to exploit the cellular DNA damage response machinery for its own efficient replication and for apoptosis induction, further extending our understanding for the molecular mechanism of PCV2 infection.
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Quan
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Zixue
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.affiliation: Laboratory of Functional Proteomics and Research Center of Reverse Vaccinology, College of Veterinary Medicine, Hunan Agricultural University, Furong District, Changsha 410128, China.
authors.forename: Naidong
authors.initials: N
authors.lastname: Wang
authors.affiliation: Laboratory of Functional Proteomics and Research Center of Reverse Vaccinology, College of Veterinary Medicine, Hunan Agricultural University, Furong District, Changsha 410128, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002478:Cells, Cultured; D018173:Circoviridae Infections / Q000235:genetics; D017925:Circovirus / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D051747:DNA-Activated Protein Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D051716:Replication Protein A / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013552:Swine; D014779:Virus Replication / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051716:Replication Protein A; D011065:Poly(ADP-ribose) Polymerases; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; D053148:Caspase 3