title: Glutamine starvation enhances PCV2 replication via the phosphorylation of p38 MAPK, as promoted by reducing glutathione levels.
abstract: Glutamine has a positive effect on ameliorating reproductive failure caused by porcine circovirus type 2 (PCV2). However, the mechanism by which glutamine affects PCV2 replication remains unclear. This study was conducted to investigate the effects of glutamine on PCV2 replication and its underlying mechanisms in vitro. The results show that glutamine promoted PK-15 cell viability. Surprisingly, glutamine starvation significantly increased PCV2 replication. The promotion of PCV2 replication by glutamine starvation disappeared after fresh media with 4 mM glutamine was added. Likewise, promotion of PCV2 was observed after adding buthionine sulfoximine (BSO). Glutamine starvation or BSO treatment increased the level of p38 MAPK phosphorylation and PCV2 replication in PK-15 cells. Meanwhile, p38 MAPK phosphorylation and PCV2 replication significantly decreased in p38-knockdown PK-15 cells. Promotion of PCV2 replication caused by glutamine starvation could be blocked in p38-knockdown PK-15 cells. Therefore, glutamine starvation increased PCV2 replication by promoting p38 MAPK activation, which was associated with the down regulation of intracellular glutathione levels. Our findings may contribute toward interpreting the possible pathogenic mechanism of PCV2 and provide a theoretical reference for application of glutamine in controlling porcine circovirus-associated diseases.
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. cxx@njau.edu.cn.
authors: Xingxiang
authors: X
authors: Chen
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. 476985567@qq.com.
authors: Xiuli
authors: X
authors: Shi
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. 317162753@qq.com.
authors: Fang
authors: F
authors: Gan
authors: Department of Chemistry, Rice University, Houston, Texas, 77005, USA. da.huang@rice.edu.
authors: Da
authors: D
authors: Huang
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. khhuang@njau.edu.cn.
authors: Kehe
authors: K
authors: Huang
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002460:Cell Line; D018173:Circoviridae Infections / Q000662:veterinary* / Q000821:virology; D017925:Circovirus / Q000502:physiology*; D005973:Glutamine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D010766:Phosphorylation; D034421:Sus scrofa; D013552:Swine; D013553:Swine Diseases / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000963:Antimetabolites; D005973:Glutamine; D019328:Buthionine Sulfoximine; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione