Summary : Most DNA viruses use the nuclear environment to replicate their genomes. The nuclear envelope (NE) is a major barrier on the way into the nucleus. This requires strategies for genome delivery as DNA nuclear import is not a physiological process. Inside the nucleus the compacted “transport” form of the vDNA has to reach the site of transcription/replication by tethering the vDNA to specific host chromatin. Transcription/replication than requires conversion of the vDNA into open chromatin while retaining the need to prevent vDNA from cellular sensors and antiviral effectors.
In this project we ask; What happens to viral genomes after nuclear delivery and prior to replication? We use adenoviruses (AdV) and more recently polyoma viruses (BKV) and ask how they initially i) release their vDNA from the protective capsid, ii) transport the released vDNA to the site of transcription/replication, iii) tether the vDNA inside the nucleus and engage in chromatin reorganization to start viral gene expression/replication, iv) decompact the viral genome from a highly condensed transport form into a transcription/replication template and v) prevent antiviral sensors and effector from vDNA inactivation.
Figure 2 : Dynamic modification of adenoviral chromatin during the viral life cycle. Incoming genomes are densely packed inside the capsid into viral chromatin through the DNA binding protein VII. Imported viral genomes are decondensed, transcriptionally activated, replicated, recondensed and packaged into progeny virus. To adopt such diverse functional states viral genomes undergo dynamic chromatin remodelling using viral and cellular factors.