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Journal of Virology, October 2009, p. 10637-10643, Vol. 83, No. 20
0022-538X/09/$08.00+0 doi:10.1128/JVI.01144-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, New York 10032,1 Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece2
Received 4 June 2009/ Accepted 26 July 2009
The herpes simplex virus (HSV) ICP0 protein acts to overcome intrinsic cellular defenses that repress viral
gene expression. In that vein, viruses that have mutations in ICP0's RING finger or are deleted for the gene are sensitive to interferon, as they fail to direct degradation of promyelocytic leukemia protein (PML), a component of host nuclear domain 10s. While varicella-zoster virus is also insensitive to interferon, ORF61p, its ICP0 ortholog, failed to degrade PML. A recombinant virus with each coding region of the gene for ICP0 replaced with sequences encoding ORF61p was constructed. This virus was compared to an ICP0 deletion mutant and wild-type HSV. The recombinant degraded only Sp100 and not PML and grew to higher titers than its ICP0 null parental virus, but it was sensitive to interferon, like the virus from which it was derived. This analysis permitted us to compare the activities of ICP0 and ORF61p in identical backgrounds and revealed distinct biologic roles for these proteins.
Published ahead of print on 5 August 2009.
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