Ulf Pettersson – Mechanisms of adenovirus infection

The aim of our project is a detailed characterization of the transcriptome of the virus and that of the infected cell. For these studies, we are using state-of-the-art cDNA sequencing and proteomics technologies.

Many important discoveries have been made using human adenovirus as an experimental model for control of gene expression. Adenoviruses have moreover become of great interest as gene delivery vectors in gene therapy and as oncolytic viruses in cancer treatment.

Our results demonstrate that the adenovirus transcriptome is immensely more complex than hitherto believed with many novel splice sites. An adenovirus landmark map, showing splice and polyadenylation sites, has been constructed. The cellular genes that are up- and down regulated during the course of infection have been identified. In addition, we have identified a set of micro RNAs, which are dysregulated during an adenovirus infection. Our studies of changes in expression of so called long noncoding RNAs have resulted in some unexpected findings.

More recently our studies have been focused on changes in cellular gene expression at the protein level. Our results showed unexpectedly that there was in general a poor correlation between alterations during the infection at the RNA and protein levels. The results show that post-transcriptional control is an additional tool that the virus uses to optimize its replication. Gradually we are building up a map of the regulatory networks that operate during the different phases of the adenovirus infection.