Nuclear Retention of ICP0 in Cells Exposed to HDAC Inhibitor or Transfected with DNA Before Infection with Herpes Simplex Virus 1

The alpha (immediate early) protein ICP0 of herpes simplex virus 1 enhances the expression of genes introduced by infection or transfection. Early in infection it performs two key functions: It blocks the silencing of the viral DNA by cellular proteins and it blocks the IFN stimulated host response to infection. Between 5 and 9 h after infection, ICP0 is translocated to the cytoplasm but remains dynamically associated with proteasomes. In this report we show that in permissive cells that are poor expressors of transfected genes (HEp-2, U2OS, etc.), ICP0 is retained in the nucleus if the cells had been transfected with DNA and then infected. The retention is DNA dose- and size-dependent but not DNA type-dependent. Retention of ICP0 is also a consequence of infection with wild-type virus concomitant with exposure of cells to sodium butyrate. ICP0 is not retained in transfected/infected cells that efficiently express transfected genes (HEK293, rabbit skin cells). The retention of ICP0 in the nucleus is concordant with failure to degrade PML and disperse ND10 structures, and delays in the transition to post alpha genes expression, translocation of components of the CoREST/REST/HDAC1 complex and histone relocation in the infected cell. The data suggest that (i) retention of ICP0 is linked to its function to remodel acetylated DNA but not DNA in heterochromatin. This function is independent of response elements embedded in the DNA and (ii) transfection-resistant cells do take up DNA but process it differently than cells that readily express transfected genes.