The Role of Bovine Herpesvirus-1 Glycoprotein III in Molecular Pathogenesis and Immunomodulation.
Date of Award
Doctor of Philosophy (PhD)
Veterinary Medical Sciences - Pathobiological Sciences
Konstantin G. Kousoulas
Bovine herpesvirus-1 (BHV-1) is the pathogenic agent for infectious bovine rhinotracheitis. Current vaccines to protect against infection have serious disadvantages to producers and have been implicated in epizootic outbreaks. The virus has also been shown to cause suppression of the immune system. BHV-1 vaccines could be improved by identifying and genetically deleting those aspects of the virus responsible for immunosuppression and providing a marker within the genome which would distinguish the vaccine strain from wild types in the case of disease outbreaks. This study examined the role of gIII in viral infection and immunosuppression. This was accomplished by expressing full copy gIII and carboxy-terminal truncations of gIII in a transient eukaryotic expression system. The gene for gIII was then truncated to delete the portion of the protein showing homology to the MHC class II antigen constant domain. Glycoprotein III-derivatives were tested for their antigenic potential in lymphoproliferation assays using bovine peripheral blood mononuclear cells. Truncated versions of gIII lacking the MHC homologous region showed improved antigenic potential. Further studies using the full-copy version of gIII showed it suppressed the proliferative response to mitogen, UV-inactivated BHV-1, and other gIII derivatives. A gIII-null BHV-1 mutant, KB3305, was isolated to evaluate the effect of deleting the MHC homologous region on the virion and to provide a marker for strain identification. KB3305 replicated 10-fold less efficiently than the wild type and was approximately 15-fold more cell associated. Heparin reduced the attachment of the mutant to GBK cells by 65%, compared to 75% for the wild type. In addition, KB3305 failed to exhibit hemagglutinating activity, in contrast to the wild-type strain. In lymphoproliferation assays, KB3305 was able to stimulate an equivalent response to that induced by the wild type virus, indicating that the lack of gIII does not influence viral antigenicity.
Byrne, Katherine Marie, "The Role of Bovine Herpesvirus-1 Glycoprotein III in Molecular Pathogenesis and Immunomodulation." (1992). LSU Historical Dissertations and Theses. 5293.