Components of nuclear domain 10 bodies regulate varicella-zoster virus replication.
PML, Sp100, and Daxx are proteins that normally reside within nuclear domains 10 (ND10s). They associate with DNA virus genomes and repress the very early stages of the DNA virus replication cycle. Virus-encoded proteins counteract this innate antiviral response. ICP0, a herpes simplex virus (HSV) immediate-early protein, is necessary and sufficient to dissociate ND10s and target their two major components, PML and Sp100, for proteasomal degradation. In this report, we show that ORF61p, the varicella-zoster virus (VZV) ortholog of ICP0, does not degrade PML and alters Sp100 levels only slightly. Furthermore, we demonstrate that other virus proteins cannot substitute for this lack of function during infection. By using short interfering RNAs, we depleted PML, Sp100, and Daxx and studied their roles in plaquing efficiency, virus protein accumulation, infectious-center titer, and virus spread. The results of these studies show that components of ND10s can accelerate VZV replication but do not ultimately control cell-associated virus titers. We conclude that while both ICP0 and ORF61p activate virus gene expression, they modulate host innate repression mechanisms in two different ways. As a result, HSV and VZV commandeer their host cells by distinct mechanisms to ensure their replication and spread.
Kyratsous
Christos A
CA
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Silverstein
Saul J
SJ
D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology*; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D014645:Herpesvirus 3, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D017874:Immediate-Early Proteins; D014764:Viral Proteins