Submitted to: Developments in Biologicals
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/25/2007
Publication Date: 4/1/2008
Citation: Neill, J.D., Ridpath, J.F., Lange, A., Zuerner, R.L. 2008. Bovine Viral Diarrhoea Virus Infection Alters Global Transcription Profiles in Bovine Endothelial Cells. Developments in Biologicals (Basel). 132:93-98. Interpretive Summary: Bovine viral diarrhea virus (BVDV) is a ubiquitous virus of ruminants. Infection by these viruses can have different outcomes depending on the circumstances. If a pregnant cow is infected between 75 and 150 day of gestation, the calf may be born infected with the virus and spread it for the rest of its life. If a cow is infected, or in some cases just following vaccination with a live vaccine, the cow may have an impaired immune system for short period of time that may allow other pathogens to infect the cow or make the second infection worse. BVDV is also a major contaminant of biological reagents and cell cultures. How BVDV is able to do these things is unknown. To begin to understand what is happening, we have use serial analysis of gene expression (SAGE) to look at the gene expression patterns in normal and BVDV-infected bovine aortic endothelial cells (BAEC) to see how these patterns are affected. We found changes in the amount of proteins that affect the way in which the cell is able to respond to the viral infection as well as secondary bacterial infections. These findings will be the basis of further studies to see what role these changes play in disease caused by BVDV.
Technical Abstract: Bovine viral diarrhea viruses (BVDV) are significant pathogens of cattle worldwide. These viruses exist in both non-cytopathic and cytopathic biotypes. Non-cytopathic BVDV can establish persistent lifelong infections in cattle and are a frequent contaminant of biological reagents such as cell cultures and fetal bovine serum. We identified commercially available bovine aortic endothelial cells (BAEC) were contaminated with BVDV. To determine if BVDV alters endothelial gene transcription patterns, we used serial analysis of gene expression (SAGE) to compare gene expression profiles from uninfected and BVDV contaminated BAEC. SAGE is an open ended, quantitative method for characterizing global patterns of transcription. Comparison of expression profiles of BVDV-contaminated and noninfected cells revealed significant increases in the transcription of many genes including P-selectin, tryptophan tRNA synthetase and prostaglandin D2 synthase. These changes were validated by real-time PCR. Additionally, real-time PCR demonstrated that the response to LPS and dsRNA by contaminated cells, as well as cells acutely infected with noncytopathic BVDV, is altered. The altered response may be through the high level of expression of A20 and inhibition of activation of NF-kappaB. BAEC are commonly used as a model to study endothelial cell function in many different systems. As shown here, transcriptional, and probable protein changes resulting from BVDV infection significantly alter cellular responses, and may have a profound impact on experimental outcome. Transcriptomic analysis provided the initial clues leading to the characterization of this altered function.