- Viruses rely heavily on topoisomerases for successful replication, though their dependence on these enzymes varies based on viral genome type and replication strategy. Many viruses do not encode their own topoisomerases and instead exploit host cell enzymes to manage DNA topology during replication.
- DNA viruses, particularly large double-stranded DNA viruses like herpesviruses and poxviruses, require topoisomerase activity to resolve topological stress during genome replication. The accumulation of positive supercoils ahead of replication forks must be relieved by topoisomerases to allow continued DNA synthesis. Some large DNA viruses, like poxviruses, encode their own topoisomerases, while others depend entirely on host enzymes.
- Poxviruses are unique among viruses in encoding their own Type IB topoisomerase, which is essential for viral genome replication and transcription. This viral topoisomerase shares structural and functional similarities with eukaryotic Type IB enzymes but has distinct characteristics that make it an attractive target for antiviral therapy.
- Retroviruses, including HIV, require host topoisomerases during multiple stages of their life cycle. Integration of viral DNA into the host genome creates topological stress that must be resolved by host topoisomerases. Additionally, transcription of integrated viral genes relies on topoisomerase activity to manage DNA supercoiling.
- The relationship between viruses and topoisomerases has therapeutic implications. Topoisomerase inhibitors have shown potential as antiviral agents, particularly against DNA viruses. Understanding how viruses interact with and depend on topoisomerases has led to the development of novel antiviral strategies.
- Some viruses have evolved mechanisms to modulate host topoisomerase activity to benefit their replication. This includes altering enzyme expression levels or activity through viral proteins, demonstrating the sophisticated relationship between viruses and cellular topoisomerases.
