Microarray analysis reveals distinct signaling pathways transcriptionally activated by infection with bovine viral diarrhea virus in different cell types.

Infection with bovine viral diarrhea virus (BVDV) causes different effects depending on its biotype in vitro; cytopathogenic (cp) strains induce apoptosis, type I interferon (IFN), and various stress-mediated responses, whereas non-cytopathogenic (ncp) strains do not. However, comprehensive transcriptional profiles of the cells infected with BVDV are still unknown. Here we performed microarray analysis of BVDV-infected MDBK epithelial cells and bovine fetal muscle (BFM) fibroblast cells. Infection of both cell types with cp BVDV, but not ncp BVDV, stimulated marked up-regulation of numerous genes belonging to diverse functional classes. However, the pattern of gene expression detected in both cell types was highly distinct from each other. Notably, upon cp BVDV infection, BFM cells exhibited marked induction of IFN-stimulated genes (ISGs), whereas MDBK cells characteristically up-regulated endoplasmic reticulum stress-inducible genes, such as tribbles homolog 3 (TRB3), CHOP and asparagine synthase, and showed much weaker induction of ISGs than BFM cells. This study highlights unexpected diversity in the response of different cell types to BVDV infection.