334
Type I Interferon response in calves experimentally infected with bovine viral diarrhea virus type 1b and Mannheimia haemolytica
Bovine respiratory disease (BRD) remains one of the largest challenges facing the feedlot industry and is the leading cause of morbidity and mortality. Typically, BRD is caused by viral and bacterial co-infection. Bovine viral diarrhea virus type 1b (BVDV1b) is commonly observed in BRD cases. The BVDV genome contains a protease (Npro) which inhibits Type I Interferon (IFN) production in vitro, but in vivo, BVDV2 increased expression of Type I Interferon-stimulated genes (ISGs) in cattle fetuses that were either persistently or transiently infected. Mineral deficiencies are known to alter both immune responses and immune cell populations which could impact IFN signaling. Therefore, the objectives of the current study were to evaluate Type I Interferon response in mineral supplemented (n = 6) and mineral deficient (n = 6) calves experimentally infected with BVDV1b and Mannheimia haemolytica (MH). Diets were formulated to meet or exceed NRC (2000) nutrient requirements except for Cu, Mn, and Zn; deficient minerals were either supplemented at 150 mg of Cu, 130 mg of Mn, and 320 mg of Zn or left deficient for 46 d. After 46 d, calves were exposed to an animal persistently infected with BVDV1b for 4 d and then intratracheally challenged with MH. Peripheral blood leukocytes were collected prior to BVDV exposure (d-4), prior to MH challenge (0h), and 12 (12h) and 24 (24h) h after MH challenge. Three known ISGs, ISG15, MX1, and RTP4, were analyzed using qRT-PCR. Fold-change relative to the average d-4 value within group was calculated using the ΔΔCt method. Fold-change for each gene was the dependent variable and tested against treatment, time, and treatment x time using the MIXED procedure of SAS. There were no treatment or treatment x time interactions (P > 0.10) so treatments were pooled. There was a significant effect of time (P < 0.05) for all ISGs evaluated. At 0h, ISG15 levels increased 44-fold compared to d-4 and were 60-fold greater for both 12h and 24h (P < 0.01). Though not as robust, both RTP4 and MX1 were increased (P < 0.05) after BRD challenge with maximum induction at 12h and were 6-fold and 12-fold greater than d-4 samples, respectively. Results indicate that the Type I Interferon pathway remains active after infection with BVDV1b and mineral deficiency did not impact the Type I Interferon response.
Keywords: Interferon, Respiratory Disease, Cattle, BVDV