Technical Abstract: Efficient nutrient assimilation into useful animal-derived products is the ultimate requirement for successful animal production. Infection in young growing animals can decrease energy and nutrient use required for growth rate by redirection of nutrients to support immune defense processes. Bovine leukemia virus (BLV) infection is prevalent in several regions of the world including the US. Most BLV infections are characterized by viral latency in the majority of infected cells. Few, if any, definitive studies in cattle have addressed the potential perturbations of gene expression induced in host cells by BLV infection. This study uses integrated global gene expression information and knowledge of the regulatory events in cells to identify transcription regulation networks that control peripheral blood mononuclear cell (PBMC) responses to BLV infection. The aim is to identify the molecular and cellular pathway responses that are functioning during the viral latency stage of BLV infection. The data and regulatory network analysis indicate that CDC25A and transcription factors such as STAT1 and STAT3 may serve as important signaling pathways for the BLV-induced cellular responses. These findings provide vital information for the functional role of genes that participate in PBMC responses to BLV infection and pinpoint these newly characterized genes as potential molecular targets and biomarkers for animal infectious diseases.