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J. Virol. doi:10.1128/JVI.02308-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Replication of ICP0 null mutant herpes simplex virus type 1 is restricted by both PML and Sp100

MRC Virology Unit, Church Street, Glasgow G11 5JR, Scotland, U.K.; INSERM U522, Hôpital de Pontchaillou, Avenue Henri le Guilloux, Rennes Cedex 35033, France; Heinriche-Pette-Institute, Martinistrasse 52, Hamburg, Germany

^* To whom correspondence should be addressed. Email: r.everett{at}mrcvu.gla.ac.uk.

	Abstract

Herpes simplex virus type 1 (HSV-1) mutants that fail to express the viral immediate-early protein ICP0 have a pronounced defect in viral gene expression and plaque formation in limited passage human fibroblasts. ICP0 is a RING finger E3 ubiquitin ligase that induces the degradation of several cellular proteins. PML, the organiser of cellular nuclear sub-structures known as PML nuclear bodies or ND10, is one of the most notable proteins that is targeted by ICP0. Depletion of PML from human fibroblasts increases ICP0-null mutant HSV-1 gene expression, but not to wild type levels. In this study we report that depletion of Sp100, another major ND10 protein, results in a similar increase in ICP0-null mutant gene expression, and that simultaneous depletion of both proteins complements the mutant virus to a greater degree. Although chromatin assembly and modification undoubtedly play major roles in the regulation of HSV-1 infection, we found that inhibition of histone deacetylase activity with trichostatin A was unable to complement the defect of ICP0 null mutant HSV-1 in either normal or PML depleted human fibroblasts. These data lend further weight to the hypothesis that ND10 play an important role in the regulation of HSV-1 gene expression.

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