For several years the laboratory has been engaged in studying various aspects of the molecular biology of bovine herpes virus 1 (BHV1). The original goal of these studies was to obtain information useful for: 1) modifying BHV1 in ways which facilitated its use as a vaccine, and 2) engineering BHV1 as an expression vector for foreign genes. In pursuit of these objectives we have mapped and sequenced the thymidine kinase (TK) and glycoprotein B (gB) genes of BHV1. We have identified the TK gene as a site into which foreign genes can be inserted without inactivating the virus and have successfully expressed several foreign genes clones into this site. In addition, we have demonstrated that insertional inactivation of the TK gene (a consequence of the foreign gene insertion) results in extensive although not absolute attenuation of the virus. In all these constructions, we have used the promoter and the polyA region derived from the BHV1 gB gene to express the foreign gene. Most recently, the research interest in my laboratory has been extended to studying the role of polyadenylation in controlling gene expression in BHV1-infected cells. In mammalian cells, and the viruses which infect them, a nascent mRNA molecule is cleaved at a specific site and the newly formed 3' end of the mRNA is rapidly polyadenylated. I have recently observed that the region immediately upstream of the cleavage and polyadenylation site of 2 BHV1 genes has a pronounced effect on the activity of genes which include this region. Current studies aim to acquire information which will aid in understanding the basis of this effect and its biological relevance. |
