Host cell phosphatases in the life cycle of DNA viruses

Viruses have evolved to navigate and manipulate cellular processes in order to safeguard viral replication. The study of virus-host interactions not only sheds light on the regulation of viral life cycles but also provides means to unravel the function and therapeutic potential of cellular proteins. We have recently shown that the switch between the latent and lytic phase of the adeno-associated virus (AAV) life cycle involves inhibition of protein phosphatase 1 (PP1)-mediated dephosphorylation of chromatin regulators by the viral Rep proteins. Here we propose to further delineate the role of PP1 in the AAV life cycle. The interactions between the Rep proteins and specific PP1 holoenzymes will be explored at the molecular level and the affected cellular pathways and relevant substrates will be identified. We will apply this knowledge to improve the biological activity of AAV gene therapy vectors and explore whether the uncovered virus-host interactions can be exploited for PP1-directed therapies.

Keywords:DNA viruses, adeno-associated virus, viral life cycle, protein phosphorylation, protein phosphatases, AAV vectors

Disciplines:Cell signalling, Virology