Type I Interferon Response in Calves Experimentally Infected with Bovine Viral Diarrhea Virus Type 1b and Mannheimia Haemolytica

Bovine respiratory disease complex (BRDC) is a major health issue facing the feedlot industry and is the leading cause of morbidity and mortality in feedlot cattle. The genome of bovine viral diarrhea virus (BVDV), a common agent in BRDC, contains an amino terminus protease (Npro)that inhibits the type I interferon (IFN) response in vitro, however in vivo work indicates that thetype I IFN response is activated during BVDV infection. Dietary mineral status has been implicated in BRDC susceptibility in calves during shipping, but little is known regarding mineral supplementation and the IFN response. To determine if Cu deficiency or natural exposure to BVDV1b inhibits IFN signaling in vivo, Cu deficient (n=6) or control (n=6) calves were infected with BVDV1b and Mannheimia haemolytica (MH). Steady-state mRNA levels of MX1, ISG15, and RTP4 were determined in peripheral blood leukocytes prior to BVDV1b exposure (day -4), prior to MH challenge (0 h), and 12 h and 24 h after MH challenge. Changes in gene expression are relative to the average of day -4 values was quantified. No mineral effects were detected (P>0.10) so mineral deficient and supplemented groups were pooled. A significant time effect (P<0.05) for all interferon stimulated genes was detected. At 0h, ISG15 mRNA expression increased 44-fold and remained elevated over 60-fold for 12 h and 24 h (P<0.01). Likewise, RTP4 and MX1 increased at 12 h (P<0.05) after BRD challenge. Data suggests that regardless of Cu status, the type I interferon pathway remains active after being challenged with BVDV1b and MH in vivo.

Keywords: BVDV; Bovine respiratory disease; Interferon; Mineral; Shipping fever