Submitted to: Veterinary Microbiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/8/2003
Publication Date: 11/7/2003
Citation: Neill, J.D., Ridpath, J.F. 2003. Gene expression changes in MDBK cells infected with genotype 2 bovine viral diarrhoea virus. Veterinary Microbiology. 96(4):301-312. Interpretive Summary: Infection with bovine viral diarrhea viruses (BVDV) is a source of major economic loss to U.S. cattle producers. This is both by disease caused by BVDV and by secondary diseases that are made worse by the BVDV interfering with the immune response. Additionally, some strains of BVDV are able to infect a calf in the first trimester of pregnancy resulting in a calf that spreads the virus for the rest of its life. How the virus affects immune function and causes a persistent infection in calves is unknown. In this study, we have begun to look at what happens following infection of bovine cells with BVDV to understand how the cell responds to infection. Using serial analysis of gene expression, we looked at the genes that are expressed in normal cells and cells after infection with BVDV. We found that proteins that form the structural support of the cell were decreased in expression. Also, proteins that aid in the production of new virus were increased in production. This is the first step in understanding how the virus takes over a cell. This will give us important information about how the virus affects the function of the cell and how it is able to give rise to persistent infections.
Technical Abstract: Bovine viral diarrhea viruses (BVDV) are ubiquitous viral pathogens of cattle. These viruses exist as one of two biotypes, cytopathic and noncytopathic, based on the ability to induce cytopathic effect in cell culture. The noncytopathic biotypes are able to establish nonapparent, persistent infections in both cell culture and in bovine fetuses of less than 150 days gestation. Interactions with the host cell and the mechanism by which viral tolerance is established are 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 global, sequence-based technology, allows quantitation 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 noninfected and BVDV2-infected cell libraries revealed a number of changes in gene expression. Many of these transcriptional changes were placed into distinct biochemical pathways or functions. Isotypes of both alpha and beta tubulins were downregulated, indicating possible dysfunction in cell division and other functions were microtubules play a major role. Expression of genes encoding proteins involved in energy metabolism were expressed at essentially equivalent levels in both infected and noninfected cells. Genes encoding proteins involved in protein translation and post-translational modifications, functions necessary for viral replication 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 disadvantage.