title: Vitamin D3 supplementation alleviates rotavirus infection in pigs and IPEC-J2 cells via regulating the autophagy signaling pathway.
abstract: Vitamin D had an anti-infection effect and benefited to the intestinal health. Autophagy signaling pathway was regulated by vitamin D3 to inhibit the infection of human immunodeficiency virus type-1. Rotavirus (RV) was a major cause of the severe diarrheal disease in young children and young animals. Although evidence suggested that vitamin D3 attenuates the negative effects of RV infection via the retinoic acid-inducible gene I signaling pathway, little is known of its antiviral effect whether through the regulation of autophagy. The present study was performed to investigate whether vitamin D3 alleviates RV infection in pig and porcine small intestinal epithelial cell line (IPEC-J2) models via regulating the autophagy signaling pathway. RV administration increased the Beclin 1 mRNA abundance in porcine jejunum and ileum. 5000 IU/kg dietary vitamin D3 supplementation greatly up-regulated LC3-II/LC3-I ratios and PR-39 mRNA expression under the condition of RV challenged. The viability of IPEC-J2 was significantly inhibited by RV infection. Incubation with 25-hydroxyvitamin D3 significantly decreased the concentrations of RV antigen and non-structural protein 4 (NSP4), and up-regulated the mRNA expression of Beclin 1 and PR-39 in the RV-infected IPEC-J2 cells. And then, based on the 25-hydroxyvitamin D3 treatment and RV infection, LC3-II mRNA expression in cells was inhibited by an autophagy inhibitor 3-methyladenine (3-MA). Bafilomycin A1 (Baf A1, a class of inhibitors of membrane ATPases, inhibits maturation of autophagic vacuoles) treatment numerically enhanced the LC3-II mRNA abundance, but had no effect on NSP4 concentration. Furthermore, 25-hydroxyvitamin D3 decreased the p62 mRNA expression and increased porcine cathelicidins (PMAP23, PG1-5 and PR-39) mRNA expression in the RV-infected cells. Taken together, these results indicated that vitamin D3 attenuates RV infection through regulating autophagic maturation and porcine cathelicidin genes expression.
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tian
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Liang
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Daiwen
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Xiangbing
authors.initials: X
authors.lastname: Mao
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014, China. Electronic address: ybingtian@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D054804:Cathelicidins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D007082:Ileum; D007583:Jejunum; D018942:Macrolides / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012401:Rotavirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D012400:Rotavirus Infections / Q000188:drug therapy* / Q000235:genetics / Q000662:veterinary* / Q000821:virology; D000071456:Sequestosome-1 Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D014118:Toxins, Biological / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D000071186:Beclin-1; D054804:Cathelicidins; D006023:Glycoproteins; D018942:Macrolides; D008869:Microtubule-Associated Proteins; C081369:NS28 protein, rotavirus; D012333:RNA, Messenger; D000071456:Sequestosome-1 Protein; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D002762:Cholecalciferol; C025946:3-methyladenine; C040929:bafilomycin A1; D000225:Adenine
keywords: Autophagy; IPEC-J2 cells; Pig; Porcine cathelicidin; Rotavirus; Vitamin D(3)