Characterization of the fitness of adenoviral E1A exon 1 deletion mutants and the role of SUMOylation in DREF function

Abstract

Early region 1A (E1A) protein is the first protein expressed during the progression of adenoviral infection. E1A proteins push terminally differentiated cells back into the cell cycle through both altered cellular gene expression and activation of viral genes to start viral replication. E1A deletion mutant viruses have been used as reagents in a multitude of studies. My studies have characterized the viral growth, cytopathic effect (CPE), and viral genome replication of E1A exon 1 deletion mutants and revealed a mutant that both grows and replicates genomes at a higher rate than wildtype. The previous discovery of cellular transcription factor DREF being SUMOylated and this SUMOylation increasing globally during adenovirus infection warranted further study. My studies have shown that adenoviral growth is positively impacted by DREF SUMOylation and that expression of interferon stimulated genes (ISGs) and p53-related genes (PRGs) are affected by DREF SUMOylation in both healthy and adenoviral infected cells. This work allows for further characterization and specific use of E1A exon 1 deletion mutants and additional investigations into the role of DREF and its SUMOylation on the expression of anti-viral genes including ISGs and PRGs.