Structure and organization of the left-terminal DNA regions of fastidious adenovirus types 40 and 41

Abstract

To determine whether differences in structure and organization of the transforming regions of Ad40 and Ad41 could explain the fastidious growth of these viruses, we have sequenced these regions and analyzed the structure of the corresponding mRNAs. These regions are 85% homologous to each other and exhibit 52% of homology to the analogous Ad5 region. Like the other adenoviruses, the Ad40 and Ad41 transforming regions contain two transcriptional units, E1a and E1b. Differences and similarities in the strategic sequences of these transcription units and Ad5 regulatory elements are discussed. Northern blotting and S1-nuclease analysis of RNA isolated from transformed cells reveal that in Ad40-transformed cells region E1a is transcribed into three partially overlapping mRNAs, while no transcription of region E1b can be detected. In Ad41-transformed cells only one E1a mRNA is found, comparable to the larger Ad40 E1a mRNA. In the Ad41 E1b region a single mRNA species is synthesized, which is comparable to the E1b messenger found in cells transformed by other adenovirus serotypes. Comparison of the large proteins encoded by the Ad40 and Ad41 E1a regions with the corresponding Ad5 E1a protein shows a relatively low homology in three conserved regions. These results are discussed in relation to the transforming capacity and the fastidious growth of Ad40 and Ad41 in conventional cell lines.