title: Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells.
abstract: Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gan
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Xue
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Da
authors.initials: D
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Qian
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Junfa
authors.initials: J
authors.lastname: Hu
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Xingxiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
authors.forename: Kehe
authors.initials: K
authors.lastname: Huang
mesh_terms: D000818:Animals; D000975:Antioxidants; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation; D002478:Cells, Cultured; D018173:Circoviridae Infections / Q000139:chemically induced / Q000378:metabolism* / Q000821:virology; D017925:Circovirus / Q000187:drug effects / Q000472:pathogenicity*; D005978:Glutathione / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009793:Ochratoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D051140:Selenoproteins / Q000378:metabolism*; D013552:Swine; D013553:Swine Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D051267:NF-E2-Related Factor 2; D009793:Ochratoxins; D017382:Reactive Oxygen Species; D051140:Selenoproteins; C025589:ochratoxin A; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione
keywords: ochratoxin A; overexpression of selenoprotein S; oxidative stress; p38 signaling pathway; porcine circovirus type 2