Transcriptomic analysis of responses to cytopathic bovine viral diarrhea virus-1 (BVDV-1) infection in MDBK cells

• BVDV-1 activates transcription of multiple signaling cascades.
• BVDV-1 increases the expression of transcripts involved in the Wnt pathway.
• A meta-transcriptomic analysis is the starting point for understanding an infectious process.

The bovine viral diarrhea virus (BVDV) is responsible for significant economic losses in the dairy and cattle industry; however, little is known about the protective and pathological responses of hosts to infection. The present study determined the principal molecular markers implicated in viral infection through meta-transcriptomic analysis using MDBK cells infected for two hours with a field isolate of BVDV-1. While several immune regulator genes were induced, genes involved in cell signaling, metabolic processes, development, and integrity were down-regulated, suggesting an isolation of infected cells from cell-to-cell interactions and responses to external signals. Analysis through RT-qPCR confirmed the expression of more than one hundred markers. Interestingly, there was a significant up-regulation of two negative NF-κB regulators, IER3 and TNFAIP3, indicating a possible blocking of this signaling pathway mediated by BVDV-1 infection. Additionally, several genes involved in the metabolism of reactive oxygen species were down-regulated, suggesting increased oxidative stress. Notably, a number of genes involved in cellular growth and development were also regulated during infection, including MTHFD1L, TGIF1, and Brachyury. Moreover, there was an increased expression of the genes β-catenin, caprin-2, GSK3β, and MMP-7, all of which are crucial to the Wnt signaling pathway that is implicated in the embryonic development of a variety of organisms. This meta-transcriptomic analysis provides the first data towards understanding the infection mechanisms of cytopathic BVDV-1 and the putative molecular relationship between viral and host components.