Background Zinc (Zn) supplementation has been shown to reduce the incidence of diarrhea and to protect animals from intestinal diseases, but the mechanisms of this protective effect against virus infection in vivo have not yet been elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets with an age-dependent decrease of severity. Results We used 60 weaned piglets that were divided into three groups to evaluate the effect of different Zn levels added to a conventional diet (50 mg Zn/kg diet, Zn low , control group). The other groups received the diet supplemented with ZnO at final concentrations of 150 mg Zn/kg diet (Zn med ), or 2,500 mg/kg diet (Zn high ). Oral challenge infection with TGEV was performed when the pigs had been fed for 1 week with the respective diet. Half of the piglets of each group were sacrificed at day 1 and 18 after challenge infection. Fecal consistency was improved and body weights increased in the Zn high group when compared to the other groups, but no direct effect of Zn concentrations in the diet on fecal TGEV shedding and mucosal immune responses was detectable. However, in the Zn high group, we found a prevention of villus atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium. Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon ( IFN )- α , oligoadenylate synthetase ( OAS ), Zn transporter SLC39A4 ( ZIP4 ), but up-regulation of metallothionein-1 ( MT1 ), as well as the Zn transporters SLC30A1 ( ZnT1 ) and SLC30A5 ( ZnT5 ). In addition, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level in the Zn high but not the other groups. Finally, in the Zn high group, we documented an earlier and higher systemic TGEV-specific serum antibody response. Conclusions These results suggest that high dietary Zn could provide enhanced protection in the intestinal tract and stimulate the systemic humoral immune response against TGEV infection.
【저자키워드】 coronavirus, cytokine, Electrophysiology, zinc oxide, transmissible gastroenteritis virus, Morphometry, Zinc transporters, 【초록키워드】 Apoptosis, Zinc, Diseases, severity, Infection, interferon, diarrhea, response, IFN, oral, humoral immune response, virus infection, incidence, TGEV, group, in vivo, epithelial, mechanism, protective effect, Concentration, fecal, physiological, chloride, control group, secretion, Final, down-regulation, intestinal tract, SLC39A4, mucosal immune, villus, OAS, decrease, intestinal, PROTECT, Result, shown, addition, detectable, receiving, was performed, added, cause, reduce, groups, stimulate, evaluate the effect, serum antibody response, three group, Fecal consistency, SLC30A1, SLC30A5, 【제목키워드】 Infection, virus, gastroenteritis, mitigate,