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The therapeutic application of zinc (Zn) to treat or prevent various pathogens has been investigated in different experimental settings, but there is no report on the proposed effects of Zn treatment on virus infection in pigs. We investigated the potential benefits of Zn oxide (ZnO) in protecting pigs from infections with two important porcine viral pathogens: porcine reproductive and respiratory syndrome virus (PRRSV), which causes respiratory tract and persistent systemic infections and transmissible gastroenteritis virus (TGEV), which causes enteric infections.
In a first challenge experiment, we determined the influence of dietary ZnO supplementation on vaccination and challenge infection with PRRSV. Pigs were fed with three different diets containing no additional ZnO (natural Zn content: 50 ppm; Znlow = control group), supplemented with medium levels of ZnO (150 ppm, Znmed), or high levels (2,500 ppm, Znhigh) and half of the pigs were prime-only vaccinated with an experimental inactivated vaccine.
We found no influence of either diets or vaccination on the clinical course of PRRS, apart from an increased weight gain after infection in Znmed and Znhigh groups, when compared to Znlow group. Treatment with higher doses of ZnO resulted in slightly higher levels of PRRSV-specific antibody at 4, 7 and 21 dpi as well as neutralizing antibodies at 35 dpi. Virus-specific IFN-γ responses were not altered by vaccination and diets, whereas Znhigh supplementation increased the percentage of γδ T cells in both vaccinated and non-vaccinated animals. Feeding higher Zn diets had no effect on viral loads and/or shedding. The results in this work suggested that feeding high levels of Zn had marginal effects on humoral and cellular immune responses, but did not positively affect clinical disease and virus loads, and did not improve immune responses to vaccination with an inactivated vaccine.
Since Zn supplementation has been shown to reduce the incidence of diarrhea in the weaning period, we evaluate the protective effect of the same three diets, as used in the PRRSV challenge trial, against an important porcine enteric virus, TGEV, in a second experimental challenge experiment. Weaned piglets were orally infected with TGEV at the age of 28 days, when the piglets had been fed for 1 week with the respective diets. Piglets were sacrificed on day 1 and day 18 after challenge infection. Fecal consistency was improved and body weights were increased in the Znhigh group when compared to the other groups, but there was no effect of Zn treatments on mucosal immune responses. In the Znhigh group we also observed an earlier and higher TGEV-specific antibody response and decreased caspase-3-mediated apoptosis of jejunal epithelium and a prevention of villus atrophy, as well as down-regulation of interferon (IFN)-α, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but up-regulation of metallothionein-1 (MT), Zn transporters SLC30A1 (ZnT1) and SLC30A5 (ZnT5). Finally, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level in the Znhigh but not the other groups. The results from this TGEV challenge trials indicated that high dietary Zn could provide enhanced protection against TGEV infection in the intestinal tract.
Based on these two challenge trials in pigs, we concluded the following regarding the effects of elevated Zn levels in the diet:
1. High doses of dietary ZnO could partly improve clinical performance in both PRRSV and TGEV challenge infections;
2. ZnO supplementation had no effect on viral loads and shedding in PRRSV challenge trial;
3. Feeding high levels of ZnO had only marginal effects on systemic humoral immune responses in both challenge trials, but had no effect on mucosal immune response in the TGEV challenge trial;
4. Supplementation of diet with high levels of ZnO could suppress apoptosis in intestinal epithelial cells and prevent the disruption of the intestinal barrier integrity in TGEV challenge infection;
5. Feeding higher ZnO had no adjuvant effect of vaccination with an experimental inactivated PRRSV vaccine.