No description available.

Thesis (Ph.D.)--Murdoch University, 2005. / Thesis submitted to the Division of Health Sciences. Bibliography: leaves 161-196.

Thesis (M.S. in veterinary science)--Washington State University, May 2010. / Title from PDF title page (viewed on June 29, 2010). "College of Veterinary Medicine." Includes bibliographical references (p. 20-26).

Jembrana disease virus (JDV) is a lentivirus causing an acute infection with a 17% case fatality rate in Bali cattle in Indonesia. Control of the disease is currently achieved by identification of infected areas and restriction of cattle movement. A detergent-inactivated whole virus tissue-derived vaccine is sometimes employed in affected areas. This thesis reports initial attempts to produce genetically engineered vaccines to replace the inactivated tissue-derived vaccine, which as it is made from homogenised spleen of infected animals, is expensive to produce and could contain adventitious agents present in the donor animals. 4 potential DNA vaccine constructs were created containing the JDV genes coding for the Tat, capsid (CA), transmembrane (TM) and surface unit (SU) proteins in a commercially available vaccine plasmid. These were assessed for functionality in a range of in vitro and in vivo assays. All proteins were expressed in vitro and administration of 2 of the constructs by a commercial ‘gene gun’ into the epidermis of mice resulted in antibody production to the appropriate protein. Due to the difficulties of licensing such a DNA vaccine in Indonesia, these vaccines were not progressed further. A mathematical model was developed to describe the progression of the acute phase of Jembrana disease following experimental infection with JDV. The model divided the disease into 6 phases based on the rates of viral replication and clearance calculated from data on sequential plasma viral RNA load detected by quantitative reverse-transcription polymerase chain reaction. This allowed statistical comparison of each phase of the disease and comparison of the severity of the disease process in groups of animals. The use of the model overcame the difficulty of comparing the disease in different animals as a consequence of the animal-to-animal variation in the disease process. The mathematical model was used to identify differences in the pathogenicity of 2 strains of JDV. One strain, JDVTAB caused a more rapid onset of disease in non-vaccinated controls, a significantly higher virus load at the onset of the febrile period and a higher peak viraemia than in animals infected with JDVPUL. This provided the first evidence of variation in pathogenicity of JDV strains. The measurement of virus load also demonstrated that some JDV infected animals developed a clinical disease that was not typical of that which had been reported previously. When infected with less than 1,000 infectious virus particles, up to 20% of infected animals failed to develop a febrile response. Infection of these animals was confirmed, however, by the detection of a high titre of circulating virus particles in plasma. These atypical infections had not been reported previously. Application of the mathematical model describing the progression of the disease in individual animals was used to examine the effect of vaccination with the inactivated tissue-derived vaccine on the progression of the disease. Several effects were noted in vaccinated animals that were subsequently infected with JDV: a reduction in the duration of the febrile response, a reduction in the severity of the febrile response in the early phases of the acute disease, and a reduction in virus load in the early and later phases of the disease process. The effect of vaccination with recombinant Tat, matrix (MA) and CA protein vaccines expressed in a bacterial expression system on subsequent JDV infection was also examined. A vaccine incorporating recombinant Tat and CA vaccine emulsified with Freund’s incomplete adjuvant decreased the febrile response particularly in the later stages of the acute disease process, decreased the severity of the leucopenia in the later phases of the acute disease, and decreased the virus load in some but not all phases of the acute disease process. Vaccines administered with Freund’s incomplete adjuvant were more efficacious than vaccines administered with QuilA, the latter actually exacerbating the disease process in vaccinated animals.

Thesis (Ph.D.)--Murdoch University, 2006. / Thesis submitted to the Division of Health Sciences. Bibliography: leaves 140-174.

Thesis (Ph.D.)--Murdoch University, 2007. / Thesis submitted to the Division of Health Sciences. Includes bibliographical references (leaves 170-199).

No description available.

Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Joseph M. Le Doux; Committee Member: Andrés J. Garcia; Committee Member: Cheng Zhu; Committee Member: Nael McCarty; Committee Member: Richard Compans. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2003. / "16th September 2002." Accompanying CD contains 2 MPEG clips with accompanying text, and a copy in PDF format of: Recovery of airway cystic fibrosis transmembrane conductance regulator function in mice with cystic fibrosis after single-dose lentivirus-mediated gene transfer / M. Limberis ... [et al.], published in Human gene therapy vol. 13 (2002). Bibliography: leaves xxix-li.

Clonally derived liver tumours and an ovarian cyst developed in mice following EIAV and FIV delivery in utero. LAM PCR and 454 sequencing was used to retrieve proviral insertion sites. TaqMan analysis revealed gene expression changes in lentiviral infected tumours. STRING and IPA networks identified links between genes flanking the lentivirus provirus and oncogenic pathways supporting the role of insertional mutagenesis in Hepatocellular Carcinoma (HCC). Global methylation analysis demonstrated increased relative methylation levels in lentivirus (EIAV, FIV, and HIV) infected normal and tumour samples. This provided strong evidence for host defence against lentivirus infection by epigenetic means. Microarray data showed altered expression of Dnmt1 and Dnmt3b and TaqMan analysis revealed specific changes in Dnmts levels when compared to uninfected liver. The evidence found for involvement of DNA methylation associated with lentivirus infection and possibly tumour development required that this study be repeated in vitro. DNA methylation was investigated at early time points after lentivirus and retrovirus infection in HepG2 cells. Results revealed sharp increases in global methylation and Dnmt levels at 24 and 30hrs post infection. E2F targets play a key role in the regulation of gene expression and aberrations result in the development of cancer. Of the 94 E2F target genes analysed 77.7% were involved in DNA damage and repair mechanisms, 21.3% were known oncogenes or shown to exert oncogenic activity and 80.9% were categorised as HCC target genes. The fact that all lentiviral/retroviral vectors used in this study were found to cause changes in methylation and gene expression in vivo and in vitro suggests that these vectors, at least in the mouse, are genotoxic. Findings here support the use of the fetal animal model to identify vector genotoxicity and the mechanisms of lentiviral vector-induced tumorigenesis. This model may be a valuable tool to evaluate the safety of lentiviruses for gene therapy.