The SP100 component of ND10 enhances accumulation of PML and suppresses replication and the assembly of HSV replication compartments

Proc Natl Acad Sci U S A. 2017 May 9;114(19):E3823-E3829. doi: 10.1073/pnas.1703395114. Epub 2017 Apr 24.

Abstract

Nuclear domain 10 (ND10) bodies are small (0.1-1 μM) nuclear structures containing both constant [e.g., promyelocytic leukemia protein (PML), SP100, death domain-associated protein (Daxx)] and variable proteins, depending on the function of the cells or the stress to which they are exposed. In herpes simplex virus (HSV)-infected cells, ND10 bodies assemble at the sites of DNA entering the nucleus after infection. In sequence, the ND10 bodies become viral replication compartments, and ICP0, a viral E3 ligase, degrades both PML and SP100. The amounts of PML and SP100 and the number of ND10 structures increase in cells exposed to IFN-β. Earlier studies have shown that PML has three key functions. Thus, (i) the interaction of PML with viral components facilitates the initiation of replication compartments, (ii) viral replication is significantly less affected by IFN-β in PML-/- cells than in parental PML+/+ cells, and (iii) viral yields are significantly lower in PML-/- cells exposed to low ratios of virus per cell compared with parental PML+/+ cells. This report focuses on the function of SP100. In contrast to PML-/- cells, SP100-/- cells retain the sensitivity of parental SP100+/+ cells to IFN-β and support replication of the ΔICP0 virus. At low multiplicities of infection, wild-type virus yields are higher in SP100-/- cells than in parental HEp-2 cells. In addition, the number of viral replication compartments is significantly higher in SP100-/- cells than in parental SP100+/+ cells or in PML-/- cells.

Keywords: ICP0; ICP8; replication compartments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism*
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Cell Nucleus Structures / genetics
  • Cell Nucleus Structures / metabolism*
  • Cell Nucleus Structures / virology
  • Chlorocebus aethiops
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Promyelocytic Leukemia Protein / genetics
  • Promyelocytic Leukemia Protein / metabolism*
  • Simplexvirus / physiology*
  • Vero Cells
  • Virus Assembly / physiology*

Substances

  • Antigens, Nuclear
  • Autoantigens
  • CALCOCO2 protein, human
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • SP100 protein, human
  • PML protein, human