The Role Of Icpo In Counteracting Intrinsic Cellular Resistance To Virus Infection

In recent years it has become apparent that, in addition to the acquired and innate defences against virus infection, there is also a third aspect to antiviral defences that operates at the intracellular level. This concept is known as intrinsic resistance, intrinsic antiviral defence or intrinsic immunity. Its key features include constitutively expressed cellular proteins that restrict viral gene expression, and viral regulatory proteins that counteract the actions of the cellular inhibitors. This chapter reviews the cellular proteins and pathways that are thought to be involved in intrinsic resistance to HSV-1 infection, and the mechanisms by which these are inactivated by ICPO, an important viral regulatory protein. The phenotype of ICPO null mutant HSV-1 is described to give a background to the phenomenon, then the principal properties of ICPO itself are summarized. The effects of ICPO on components of cellular nuclear structures known as ND10 or PML nuclear bodies are reviewed, then the possible roles of these proteins in intrinsic resistance are discussed. The relationships between ICP0, intrinsic resistance and the regulation of viral chromatin structure are considered, and finally the parallels between ICP0 and related proteins expressed by other alphaherpesviruses are described. Intrinsic resistance and the manner in which viruses overcome it are important aspects of the biology of virus infection, but we have much to learn before we achieve a complete understanding of the viral and cellular proteins that are involved.