The Evolutionary Potential of Bovine Viral Diarrhea Virus: A Model ssRNA Virus
Abstract
Single stranded RNA viruses are a group of pathogens infecting all animals. They include human pathogens such as human immunodeficiency virus, hepatitis C virus and influenza. Their error-prone replication generates mutations in their genomes, producing a reservoir of viral genomes capable of surviving variable selective pressures. Under certain conditions this is called a quasispecies. Studying these viral populations in vivo is challenging and model systems help to better understand their behavior.
Bovine viral diarrhea virus (BVDV) is a ssRNA virus infecting cattle worldwide. Persistent BVDV infections, where animals are born immunotolerant to the virus due to an in utero infection, present a unique opportunity to study a quasispecies in the relative absence of immune selection. Methods and results useful for understanding both BVDV and ssRNA viruses in general are presented here.
Canadian BVDV isolates were used to infer the evolutionary history of BVDV. Significant variability in circulating isolates was observed and clustering below the sub-genotype level may be of antigenic significance. Within a single, persistently infected host, substantial clustering of viral genomes by tissue compartment was described. The variable regions of the viral genome were also conserved from animal to animal; whether a region is variable or not appears to primarily be a feature of the virus, not the host.
Preliminary data using a high-throughput viral neutralization assay showed potential to rapidly phenotype viral isolates and directly compare their antigenic properties. Although additional work is needed to ensure the assay is reproducible and reliable, statistical analysis of the data in conjunction with viral genome sequences offers a method of correlating genotype with antigenic phenotype.
These data can improve BVDV control programs, especially the design of new vaccines. More broadly, these methods and results are also applicable to other ssRNA viruses. Data describing the intrahost variation of BVDV can be applied to viruses that have persistent phases or depend on the variation generated in infected hosts to escape acquired immune responses in a host population. This thesis presents findings that both further our understanding of an important pathogen of cattle and an important group of viruses in general.
Description
Keywords
Bioinformatics, Genetics, Biology--Molecular, Veterinary Science, Virology
Citation
Chernick, A. A. (2016). The Evolutionary Potential of Bovine Viral Diarrhea Virus: A Model ssRNA Virus (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28139