Gene expression changes in BVDV2-infected MDBK cells

Abstract

Bovine viral diarrhoea virus (BVDV) is a ubiquitous viral pathogen of cattle. The virus exists as one of two biotypes, cytopathic and non-cytopathic, based on the ability to induce cytopathic effect in cell culture. The non-cytopathic biotypes are able to establish non-apparent, persistent infections in both cell culture and in bovine foetuses of fewer than 150 days gestation. The mechanism by which viral tolerance is established is unknown. To examine the changes in gene expression that occur following infection of host cells with BVDV, serial analysis of gene expression (SAGE), a global gene expression technology was used. SAGE, a sequence-based technology, allows quantification of virtually every transcript in a cell type without prior sequence information. Transcript expression levels and identities are determined by DNA sequencing of libraries composed of 14 base DNA fragments (tags) derived from the 3′ end of each cellular mRNA transcript. Comparison of data obtained from non-infected and BVDV2-infected cell libraries revealed a number of changes in gene expression. Many of these transcriptional changes could be placed into distinct biochemical pathways or functions. Both α and β tubulins were downregulated, indicating possible dysfunction in cell division and other functions where microtubules play a major role. Expression of several genes encoding proteins involved in energy metabolism were downregulated, indicating possible decreased ATP synthesis. Genes encoding proteins involved in protein translation and post-translational modifications were generally upregulated. These data indicate that following infection with BVDV, changes in gene expression occur that are beneficial for virus replication while placing the cell at a metabolic disadvantage.