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|Title:||Cloning and Molecular Characterization of Novel Animal Papillomaviruses|
|Author(s):||O'banion, Michael Kerry|
|Department / Program:||Microbiology|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Abstract:||Papillomaviruses represent a diverse group of species and tissue specific viruses which are important agents of disease, including some cancers. This thesis describes the cloning and molecular characterization of five new animal papillomaviruses: an equine cutaneous papillomavirus (EqPV); a canine oral papillomavirus associated with vaccine-induced carcinomas (COPV); an avian papillomavirus (PePV); an oral papillomavirus of domestic rabbits (ROPV); and the first papillomavirus isolated from a murine species, Micromys minutus, which is associated with carcinomas in the natural host (MmPV). In addition, the existence of two other papillomaviruses in genital lesions of a horse and a monkey was established.
Characterization of each cloned virus involved generation of a restriction map, orientation of the genome to characterized DNAs of other papillomavirus by hybridization or sequence analysis, and comparison of the DNA of the new virus to other papillomavirus DNAs. The comparative studies were extended in the case of ROPV to include partial sequencing since ROPV showed significant DNA homology with the cottontail rabbit papillomavirus and two human papillomaviruses: HPV-1a, associated with plantar warts, and HPV-16, associated with cervical carcinomas. The significance of these comparisons is discussed. In addition, the five new papillomavirus clones were used in a large comparative analysis with 23 different papillomaviruses in an attempt to correlate biological phenotype with homologies at the DNA level. An association among those viruses which induce fibroblast proliferation and among those with epithelial tropism was observed.
Three of the five new viral DNAs were used for transfection of mouse tissue culture cells; however, no evidence of morphologic transformation was observed though some viral DNAs appeared to replicate. Finally, the DNAs of EqPV, COPV, and MmPV were used as molecular probes against neoplasms in their respective hosts. COPV DNA was demonstrated in squamous cell carcinomas occurring in dogs inoculated with a live papillomarvirus vaccine. MmPV DNA was observed in a variety of skin tumors from harvest mice as well as in "normal" tissues from individuals with lesions elsewhere.
The isolation of a mouse papillomavirus presents a possibility for the development of an animal model to study the oncogenic potential of these viruses in vitro. In addition to providing new systems, the results described here underscore the diverse nature of these important viruses.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1987.
|Date Available in IDEALS:||2014-12-16|