Abstract
In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral replication at different stages. The antiviral function of ND10, however, is antagonized by viral regulatory proteins (e.g., ICP0 of herpes simplex virus; IE1 of human cytomegalovirus) which induce either a modification or disruption of ND10. This review will summarize the current knowledge on how viral replication is inhibited by ND10 proteins. Furthermore, herpesviral strategies to defeat this host defense mechanism are discussed.
Highlights
Viruses depend in many aspects on the cellular machinery in order to replicate efficiently
15 years ago a subnuclear structure known as nuclear domain 10 (ND10; alternatively termed PML-NBs for PML nuclear bodies or PODs for PML oncogenic domains) has been discovered that is targeted by a variety of viruses belonging to different viral families
It functions as a kind of scaffold protein that is responsible for the assembly and maintenance of PML-NBs and recruits other ND10-associated proteins like hDaxx to this subnuclear structure [12,13]
Summary
Viruses depend in many aspects on the cellular machinery in order to replicate efficiently. Viruses have evolved in tight association to the host cell to be able to hijack the cellular apparatus that is necessary for their replication. It could be shown that a set of constitutively expressed cellular proteins, collectively termed intrinsic immunity, represents one of the first lines of antiviral defense in naive hosts [1]. The main objective of this article is to critically discuss the very recent literature on the role of ND10 for viral infection. It will focus on herpesviruses, since these have been most extensively studied with respect to the functional consequences of ND10 association. The diverse strategies herpesviruses have evolved to overcome this ND10-based host defense are outlined
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