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Date of Award

1-1983

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Supervisor

Professor S. Mak

Abstract

The cyt mutants of the highly oncogenic adenovirus type 12 (Ad12) produce low yields of virus and are generally weakly tumorigenic. In this study, four cyt mutants examined were-shown to induce extensive degradation of DNA in infected cells. Complementation tests using two cyt mutants, host range and host range-deletion mutants of Ad5, and wild type Ad12 and Ad5 in various cell types, suggested that two viral functions are involved in the control of DNA degradation. One of these functions, a DNase-inhibitory function, mapped by genetic complementation in early region E1b of the Ad5 genome. A transcriptional study of early region E1 of the Ad12 genome identified mRNA species complementary to the left 10.5 percent of the genome by the method of RNA-blot hybridization. Ad12 appeared to possess a region E1b physically corresponding to that of Ad5, suggesting that the DNas-inhibitory function also maps in this region in Ad12. Results implicated the association of this function with an E1b-19,000 dalton polypeptide of both serotypes. The second viral function appeared to influence positively the induction of DNA degradation. This DNase-effecter function appeared to be an early viral function. Results of time course-superinfection experiments in which cyt mutant-infected cells were superinfected with wild type strains of Ad12 and Ad5 and analyzed for the properties of DNA degradation and virus yields, support the hypothesis that the degradation of DNA is determined by the relative abundance of the DNase-inhibitory factor and the DNase-effecter, and that the two factors might functionally interact with each other.

A supplementary study on the interference with the DNA replication of Ad12-strain 1131 by an Ad12-strain Huie variant, Ad12 Huie (MB), suggested that the interference capacity lies in a nucleotide sequence repeat structure at the right terminus of the Ad12-Huie (MB) genome.

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