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

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>i</i>) the interaction of PML with viral components facilitates the initiation of replication compartments, (<i>ii</i>) viral replication is significantly less affected by IFN-β in PML^-/- cells than in parental PML^+/+ cells, and (<i>iii</i>) 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.