title: Interaction of herpes simplex virus ICP0 with ND10 bodies: a sequential process of adhesion, fusion, and retention.
abstract: On entry into the nucleus, herpes simplex virus 1 (HSV-1) DNA localizes to nuclear bodies known as ND10. Gene repression imposed by ND10 is released by a viral protein, ICP0, via degradation of the ND10 constituents promyelocytic leukemia protein (PML) and Sp100 and the subsequent dispersal of ND10 bodies. In order to understand the dynamic interaction between ICP0 and ND10, we carried out deletion mapping to identify the domains of ICP0 responsible for its association with ND10. Here, we report the following. (i) An ND10 entry signal (ND10-ES), located between residues 245 and 474, is required for ICP0 to penetrate and fuse with ND10. ICP0 lacking ND10-ES adheres to the surface of ND10 but fails to enter. (ii) In the absence of ND10-ES, the E3 ubiquitin ligase of ICP0 facilitates the transient adhesion of the truncated ICP0 to the ND10 surface, whereas the presence of ND10-ES in ICP0 renders ND10 fusion regardless of the E3 ligase activity. (iii) The C terminus of ICP0 is required for retention of ICP0 in ND10 but plays no role in the recruitment process. (iv) The adverse effects of an inactive RING domain on viral replication are partially reversed by deleting either ND10-ES or the C-terminal retention domain, suggesting that additional ICP0 functions require the release of ICP0 from ND10. Based on these results, we conclude that association of ICP0 and ND10 is a dynamic process, in which three sequential steps--adhesion, fusion, and retention--are adopted to stabilize the interaction. A faithful execution of these steps defines the ultimate productivity of the virus.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, USA. haidong.gu@wayne.edu
authors.forename: Haidong
authors.initials: H
authors.lastname: Gu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
mesh_terms: D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D018259:Herpesvirus 1, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C094297:CALCOCO2 protein, human; D017874:Immediate-Early Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1