An Analysis of the Transforming Functions of Bovine Papillomavirus Type 4 in an In Vitro Assay System

Pennie, William David (1992) An Analysis of the Transforming Functions of Bovine Papillomavirus Type 4 in an In Vitro Assay System. PhD thesis, University of Glasgow.

Abstract

The transformation biology of bovine papillomavirus type 4 (BPV-4) was investigated using an in vitro assay system. In vivo the virus cooperates with bracken to cause alimentary canal carcinoma in cattle and transforms via a "hit-and-run" mechanism; viral DNA is observed in papillomas but not in the resulting tumours. Molecularly cloned BPV-4 genome and subgenomic fragments were transfected into primary bovine palate fibroblasts (PalF) and their ability to induce morphological transformation assessed. BPV-4 is incapable of transformation without the introduction of a cooperating activated ras oncogene and the resultant cells are neither immortal nor tumorigenic. The major transforming function was found to be the E7 open reading frame (ORF) with a possible role for the E8 ORF. The majority of BPV-4 transformed lines are found to lose viral DNA on passage, as observed in vivo. BPV-4 and the other BPV subgroup B viruses BPV-3 and BPV-6 lack an E6 ORF, a transforming function in other papillomaviruses. Introducing an E6 from human papillomavirus type 16 in cooperation with BPV-4 E7 leads to immortalisation. Immunocytochemistry was used to determine the cellular localisation of the transforming proteins of the virus. A possible interaction of the E8 protein with a structural component of gap junctions is demonstrated. A bracken mutagen, quercetin, is able to initiate PalF cells, allowing full malignant transformation by BPV-4 and ras.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Virology, Genetics
• Date of Award: 1992
• Depositing User: Enlighten Team
• Unique ID: glathesis:1992-78389
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:29
• Last Modified: 30 Jan 2020 15:29
• URI: https://theses.gla.ac.uk/id/eprint/78389